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Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883G>A) and rs7116432 (c.2024+779A>G) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

Few studies have addressed how selective pressures have shaped the genetic structure of the current Native American populations, and they have mostly limited their inferences to admixed Latin American populations. Here, we searched for local adaptation signals, based on integrated haplotype scores and population branch statistics, in 325 Mexican Indigenous individuals with at least 99% Native American ancestry from five previously defined geographical regions. Although each region exhibited its own local adaptation profile, only PPARG and AJAP1, both negative regulators of the Wnt/β catenin signaling pathway, showed significant adaptation signals in all the tested regions. Several signals were found, mainly in the genes related to the metabolic processes and immune response. A pathway enrichment analysis revealed the overrepresentation of selected genes related to several biological phenotypes/conditions, such as the immune response and metabolic pathways, in agreement with previous studies, suggesting that immunological and metabolic pressures are major drivers of human adaptation. Genes related to the gut microbiome measurements were overrepresented in all the regions, highlighting the importance of studying how humans have coevolved with the microbial communities that colonize them. Our results provide a further explanation of the human evolutionary history in response to environmental pressures in this region.

The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15–30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4–9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far., Indigenous populations, including in those in Mexico are underrepresented in genetic studies. Here, the authors perform a population genetics study of indigenous peoples in Mexico to explore demographic histories of the region in the context of geography and cultural influences.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 G>T and rs459552 A>T), axis inhibition protein 1 (AXIN1) (rs9921222 C>T and rs1805105 C>T), AXIN2 (rs7224837 A>G), and dishevelled 2 (DVL2) (2074222 G>A and rs222836 C>T). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

Colorectal cancer is the third cause of cancer and the second leading cause of death worldwide. The CD44 gene plays a key role in malignant processes, including growth, survival, epithelial to mesenchymal transition and metastasis. It is also known that some variants as rs187116 (c.67+4883GA) and rs7116432 (c.2024+779AG) can modulate the function of the CD44 gene and malignant transformation in several neoplasms. This study aims to explore, for the first time, the association of the CD44 rs187116 and rs7116432 variants in patients with colorectal cancer. Genomic DNA from 250 patients and 250 healthy blood donors were analyzed. The identification of variants was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test and multivariate analysis. Individuals carrying the G/A and A/A genotypes for the rs187116 polymorphism showed an increased risk for colorectal cancer (OR = 3.11, 95% CI: 1.87-5.16, P = 0.001 and OR = 3.59, 95% CI: 2.06-6.25, P = 0.001, respectively). After adjusting for age and gender, these same genotypes and the G/G genotype of the rs7116432 polymorphism were associated with TNM stage and tumor location in the colon. Moreover, the A-G (rs187116 and rs7116432) haplotype was associated with increased risk; while, the haplotype G-A (rs187116 and rs7116432) was related with decreased risk. In conclusion, our results suggest that the here analyzed CD44 variants are involved with risk, TNM stage and tumor location in colorectal cancer.

Summary Interferon‐inducible transmembrane protein 3 (IFITM3) participates in the defense against viral infections. This study identified and compared the frequency of the IFITM3 rs12252 polymorphism in 410 individuals in western Mexico. The western Mexican allelic frequencies (frequency of the “C” allele = 0.18) differ from some American, East Asian and European populations.

Gestational diabetes mellitus (GDM) is a metabolically complex disease with major genetic determinants. GDM has been associated with insulin resistance and dysfunction of pancreatic beta cells, so the GDM candidate genes are those that encode proteins modulating the function and secretion of insulin, such as that for calpain 10 (CAPN10). This study aimed to assess whether single nucleotide polymorphism (SNP)-43, SNP-44, SNP-63, and the indel-19 variant, and specific haplotypes of the CAPN10 gene were associated with gestational diabetes mellitus. We studied 116 patients with gestational diabetes mellitus and 83 women with normal glucose tolerance. Measurements of anthropometric and biochemical parameters were performed. SNP-43, SNP-44, and SNP-63 were identified by polymerase chain reaction (PCR)-restriction fragment length polymorphisms, while the indel-19 variant was detected by TaqMan qPCR assays. The allele, genotype, and haplotype frequencies of the four variants did not differ significantly between women with gestational diabetes mellitus and controls. However, in women with gestational diabetes mellitus, glucose levels were significantly higher bearing the 3R/3R genotype than in carriers of the 3R/2R genotype of the indel-19 variant (p = 0.006). In conclusion, the 3R/3R genotype of the indel-19 variant of the CAPN-10 gene influenced increased glucose levels in these Mexican women with gestational diabetes mellitus.

Polymorphisms in the LEP (G–2548A and A19G), LEPR (A326G, A668G and G3057A) and RETN (C–420G and G+62A) genes were documented according to their association with alterations in biochemical parameters such as glucose, insulin and lipid profiles, along with serum leptin and resistin concentrations. The aim of the study was to establish any contribution of the G-2548A and A19G polymorphisms of the LEP gene, the A326G, A668G and G3057A polymorphisms of the LEPR gene, and the C-420G and G+62A polymorphisms of the RETN gene to serum leptin and resistin levels in Mexican young adults. Clinical and biochemical variables, serum leptin and resistin levels, and genotype profiles were analysed in 66 Mexican young adults. Seven polymorphisms in the LEP, LEPR and RETN genes were genotyped using polymerase chain reaction–restriction fragment length polymorphisms analysis. Individuals carrying allele 3057A of the G3057A polymorphism in the LEPR gene showed significantly higher leptin concentrations than those bearing the genotype G/G (43.78 ± 39.11 vs 28.20 ± 14.12 ng/mL; p = 0.021). There were no associations of serum leptin or resistin levels according to the genotype of the other six analysed polymorphisms. Our results suggest that the allele 3057A of the LEPR G3057A polymorphism contributes to increased serum leptin levels in Mexican young adults.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. The named "destruction complex" has a critical function in the Wnt/β-catenin pathway regulating the level of β-catenin in the cytoplasm and nucleus. Alterations in this complex lead to the cellular accumulation of β-catenin, which participates in the development and progression of CRC. This study aims to determine the contribution of polymorphisms in the genes of the β-catenin destruction complex to develop CRC, specifically adenomatous polyposis coli (APC) (rs11954856 GT and rs459552 AT), axis inhibition protein 1 (AXIN1) (rs9921222 CT and rs1805105 CT), AXIN2 (rs7224837 AG), and dishevelled 2 (DVL2) (2074222 GA and rs222836 CT). Genomic DNA from 180 sporadic colorectal cancer patients and 150 healthy blood donors were analyzed. The identification of polymorphisms was made by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test. Increased susceptibility to CRC was associated with the polymorphic variants rs11954856 (APC), rs222836 (DVL2), and rs9921222 (AXIN1). Decreased susceptibility was associated with the polymorphisms rs459552 (APC) and 2074222 (DVL2). Association was also observed with advanced Tumor-Node-Metastasis (TNM) stages and tumor location. The haplotypes G-T in APC (rs11954856-rs459552) and A-C in DVL2 (rs2074222-rs222836) were associated with decreased risk of CRC, while the G-T haplotype in the DVL2 gene was associated with increased CRC risk. In conclusion, our results suggest that variants in the destruction complex genes may be involved in the promotion or prevention of colorectal cancer.

Mutations and polymorphisms of the GSK3β gene have been associated with several diseases including Alzheimer disease, diabetes and cancer; however, to date, no variants of this gene have been associated with colorectal cancer (CRC). This study aims to explore, for the first time, the association of the GSK3β rs334558 and rs6438552 polymorphisms with CRC.Genomic DNA from 330 CRC patients and healthy blood donors were analyzed. Identification of polymorphisms was made by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated by the odds ratio (OR) test.Patients carrying the C/T genotype for the rs334558 (TC) polymorphism showed an increased risk for CRC (OR = 1.71, 95% CI: 1.05-2.79, P = 0.039); this association was also observed for TNM stage and tumor location. For the rs6438552 (TC) polymorphism, the OR analysis showed that patients carrying C/T and C/C genotypes have a decreased risk for CRC (OR = 0.44, 95% CI: 0.27-0.70, P = 0.001 and OR = 0.24, 95% CI: 0.10-0.64, P = 0.001, respectively); this decreased risk was also evident in the stratified analysis by TNM stage and tumor location. Haplotype analysis of these 2 loci of GSK3β (rs334558 and rs6438552) showed differential distribution. The T-T and C-C haplotype was associated with a decreased risk of CRC, while the T-C haplotype was associated with an increased risk of CRC.Our results denote that GSK3β gene polymorphisms play a significant role in promoting or preventing CRC. Additionally, variations in this gene are associated with the tumor site and the tumor-node-metastasis (TNM) stage in these patients.

Polymorphisms in the CYP2C9 and CYP2C19 genes confer potential risk for specific adverse drug reactions and therapeutic effect failure. Their frequencies differ among ethnic groups. This study was aimed to describe the distribution of CYP2C9 and CYP2C19 alleles and haplotypes in four Mestizo populations from Western Mexico and their comparison with the reported data from other ethnic groups.The CYP2C alleles (CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3) were genotyped using polymerase chain reaction-restriction fragment length polymorphisms analyses using DNA samples from 477 healthy Mestizo individuals of Colima (n = 100), Jalisco (n = 147), Michoacán (n = 117), and Nayarit (n = 113).Frequencies ranged from 2.2-3.0% and 4.8-8.9% for CYP2C9*3 and CYP2C9*2 alleles, respectively, and 5.4-12.0% for CYP2C19*2, whereas the CYP2C19*3 allele was not found. Haplotype GACA, which harbors the loss-of-function allele CYP2C19*2, was the second most frequent (8.7%). Genetic heterogeneity between the Western Mexican populations studied here and the global population was evident (p 0.05), except for most American populations and other Mexican Mestizo populations.Our findings increase the evidence for genetic variability at relevant pharmacogenetic loci and could be useful in association studies involving drugs that are substrates for CYP2C enzymes in the Western Mexican population.

The Interleukin (IL)-1 family of cytokines plays a key role in the inflammatory response. Genes coding for IL-1α, IL-1β, and IL-1Ra are located together as a block gene known as the IL-1 cluster. This genomic region shows wide nucleotide variability, and some polymorphisms have been widely studied and associated with features related to the metabolic syndrome.Eight polymorphisms within three genes of the IL-1 cluster, including IL1A (rs3783553, rs17561, and rs1800587), IL1B (rs1143634, rs1143627, and rs16944) and IL1RN (rs419598 and rs2234663) were genotyped in 460 Mexican adolescents. Genotype and haplotype frequencies are reported, as well as the linkage disequilibrium analysis. Genetic associations with some anthropometric and metabolic traits were evaluated.Allele frequencies were similar to those found in other populations, and genotype proportions were according to the Hardy-Weinberg equilibrium. Seven haplotypes were observed at frequencies ≥5%. Of the entire cluster, only the rs17561-rs1800587 and rs1143627-rs16944 pairs showed highest and significant linkage disequilibrium values. An haplotype of IL1A, rs17561T-rs1800587T, was significantly associated with increase in body mass index in males (p0.008), whereas IL1B and IL1RN variants showed associations with insulin, and hs-CRP (p0.05).Some MetS parameters seem to be influenced by variations in the IL-1 gene cluster in Mexican adolescents. These variations may confer risk for metabolic alterations from early ages, and and these risks may be different when variables such as sex are considered. Strategies leading to generate protective behaviors could be designed to take into account specific variations in the IL-1 gene cluster and biological conditions such as sex.

Background Polycystic ovary syndrome is a complex and heterogeneous disease leading to reproductive, as well as metabolic problems. It has been suggested that there may be a genetic predisposition in the aetiology of polycystic ovary syndrome. The identification of calpain 10 gene (CAPN10) as the first candidate gene for type 2 diabetes mellitus has focused the interest in investigating their possible connection with the polycystic ovary syndrome. This syndrome is associated with hyperinsulinaemia and insulin resistance, two metabolic abnormalities associated with type 2 diabetes mellitus. Objective To investigate if there is association between the SNP-63 and the genetic variant indel-19 of CAPN10 gene and polycystic ovary syndrome in women of reproductive age. Material and methods This study included 101 women (55 with polycystic ovary syndrome and 46 without polycystic ovary syndrome). The genetic variant indel-19 was identified by electrophoresis of the amplified fragments by PCR, and the SNP-63 by PCR-RFLP. Results The allele and genotype frequencies of the two variants do not differ significantly between women with polycystic ovary syndrome and the control women group. The haplotype 21 (defined by the insertion allele of indel-19 variant and C allele of SNP-63) was found with higher frequency in both study groups, being more frequent in the polycystic ovary syndrome patients group, however, this difference was not statistically significant. Conclusions The results suggest that SNP-63 and indel-19 variant of CAPN10 gene do not represent a risk factor for polycystic ovary syndrome in our patient group.

PPARD encodes for peroxisome proliferator-activated receptor delta, which plays a significant role in controlling lipid metabolism, atherosclerosis, inflammation, cancer growth, progression, and apoptosis. Accumulated evidence suggests that the polymorphism rs2016520 in PPARD is associated with lipid metabolism, obesity, metabolic syndrome, and type 2 diabetes mellitus. The aim of this study was to determine whether the single nucleotide polymorphism +294T/C (rs2016520) in PPARD is associated with colorectal cancer (CRC) in the Mexican population. Genomic DNA from 178 CRC patients and 97 healthy blood donors was analyzed. The polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Results demonstrated that patients with the T/C genotype for the +294T/C (rs2016520) polymorphism present a protective role against CRC [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.22-0.69; P = 0.0008]. This association was also evident for the T/C genotype in the stratified analysis by tumor-node-metastasis stages I+II (OR = 0.26, P = 0.0332) and III+IV (OR = 0.44, P = 0.0067). However, in the stratified analysis by tumor location, we observed an increased risk of rectal cancer (OR = 7.57, P = 0.0403) vs colon cancer (OR = 4.87, P = 0.234) in patients carrying the C/C genotype and under the dominant and recessive models of inheritance. In conclusion, for the first time, the association between the +294T/C (rs2016520) polymorphism and colorectal cancer has been studied in Mexican patients. Our results reveal that variations in PPARD may play a significant role in genetic susceptibility to colorectal cancer.

The so-called tumor necrosis factor (TNF) block includes the TNFA, lymphotoxin alpha and beta (LTA and LTB) genes with single-nucleotide polymorphisms (SNP) and microsatellites with an allele frequency that exhibits interpopulation variability. To date, no reports have included both SNPs and microsatellites at the TNF block to study Mestizo or Amerindian populations from Mexico. In this study, samples of five Mexican Mestizo populations (Durango, Guadalajara, Monterrey, Puebla, and Tierra Blanca) and four native-Mexican populations (North Lacandonians, South Lacandonians, Tepehuanos, and Yaquis) were genotyped for two SNPs (LTA+252A>G and TNFA-308G>A) and four microsatellites (TNFa, d, e, and f), to analyze the genetic substructure of the Mexican population. Allele and haplotype frequencies, linkage disequilibrium (LD), and interpopulation genetic relationships were calculated. There was significant LD along almost all of the TNF block but the lowest D' values were observed for the TNFf-TNFd pair. Mestizos showed higher allele and haplotype diversity than did natives. The genetic differentiation level was reduced among Mestizos; however, a slightly, but significant genetic substructure was observed between northern and southern Mexican Mestizos. Among the Amerindian populations, the genetic differentiation level was significantly elevated, particularly in both North and South Lacandonians. Furthermore, among Southern Lacandonians, inhabitants of Lacanja town were the most differentiated from all the Mexicans analyzed. The data presented here will serve as a reference for further population and epidemiological studies including these TNF polymorphisms in the Mexican population.

Objectives Mexico harbours a very complex genetically diverse population composed of two main groups: Mexican Mestizos and at least 68 heterogeneous native Mexican populations. CYP2C9 and CYP2C19 polymorphisms may confer risk for specific adverse drug reactions and therapeutic effect failure, and their frequencies exhibit ethnic variability. We aimed to describe the distribution of CYP2C9 and CYP2C19 alleles and haplotypes in four Mexican indigenous populations and to compare data with those reported for other native Mexican and Amerindian populations. Methods We genotyped 459 DNA samples from healthy individuals of four native Mexican populations: Yaqui, Mixteco, North Lacandon and South Lacandon for CYP2C9*2 and CYP2C9*3 alleles using a TaqMan qPCR allelic discrimination assay, and CYP2C19*2 and CYP2C19*3 alleles using polymerase chain reaction–restriction fragment length polymorphisms (PCR–RFLP). Results Frequencies were in the range 0.7–2.4% for the CYP2C9*2 allele and 0.5–7.8% for the CYP2C9*3 allele. The CYP2C19*2 allele was found in a high frequency (range, 6.0–19.3%), while CYP2C19*3 was not found. Haplotype G A CA (CYP2C19*2–CYP2C9*1), which harbours the loss-function allele CYP2C19*2, was observed in almost all populations studied, in the range 5.9–19.3%. Genetic variability was observed mainly between northern and southern populations, both among our studied populations and among other native populations of Mexico and other Amerindians (p Conclusion This study highlights the genetic variability of the Mexican native population and, because the CYP2C19*2 allele was the most frequent in almost all our studied populations, also draws attention to the potential clinical impact of this allele in vulnerable and isolated groups such as native populations of Mexico.

Background and Aims There is evidence that family history of type 2 diabetes (FHT2D) and single nucleotide polymorphisms (SNP) on the IL-6 gene promoter region are separately associated with the risk of developing type 2 diabetes. However the relationship between adult Mexican subjects with FHT2D and genotypes/haplotypes for IL-6 gene has not been explored. The aim of the present work was to study the prevalence of IL-6 −598G>A−572G>C−174G>C haplotypes among subjects with FHT2D and to determine whether their presence influences the relationship between FHT2D and risk factors for diabetes. Methods Two hundred fifty eight nondiabetic subjects participated in this study; 153 with and 105 without FHT2D. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) was used for genotyping. Logistic regression analysis was employed to assess the impact of IL-6 haplotypes on FHT2D per se and hyperinsulinemia and insulin resistance as risk factors for diabetes. Results Subjects with FHT2D showed a higher prevalence of hyperinsulinemia and insulin resistance (IR) than those without FHT2D (14.4 vs. 5.7%, p = 0.029, and 14.2 vs. 7.0% p = 0.050, respectively). Lower prevalence of −598 -572-174 (AGC)-haplotype (19%) in subjects with FHT2D was observed as well as a lower prevalence of hyperinsulinemia and IR among AGC haplotype carriers (12 and 14%, respectively). The relationship between FHT2D and IR was modified by the presence of AGC haplotype (from OR, 2.70; 95% CI, 0.99–7.36; p = 0.050 OR, 30.08; 95% CI, 0.58–1,568.06; p = 0.092). Conclusions IL-6 −598/−572/−174 (AGC) haplotype has a low prevalence among first-degree relatives of subjects with type 2 diabetes. Our results suggest that this haplotype is associated with decreased risk of type 2 diabetes in Mexican subjects with FHT2D.

Background Gestational diabetes mellitus (GDM) is characterized by insulin resistance. It has been described that tumor necrosis factor α (TNF-α) plays a key role in the pathogenesis of insulin resistance; moreover, increased levels of this proinflammatory cytokine have been reported in women with GDM. Therefore, this study was aimed to assess the presence of associations between the -308G/A and -238G/A polymorphisms and specific haplotypes of the TNF-α gene promoter region and insulin resistance in Mexican women with GDM. Methods This study included 51 women with GDM and 44 pregnant women with normal glucose tolerance. Measurements of anthropometric parameters and biochemical estimations were performed. We genotyped the TNF-α -308G/A and -238G/A polymorphisms using polymerase chain reaction-restriction fragment length polymorphism analysis. Results The genotype and allele frequencies of both polymorphisms did not differ significantly between the women with GDM and the controls. However, we found that the frequency of the AG haplotype was significantly increased in the patients with GDM compared with controls ( P = 0.019; odds ratio, 4.11; 95% confidence interval, 1.31-12.85). In patients with GDM, we observed that insulin levels and homeostasis model assessment of insulin resistance were significantly higher in women bearing the G/G genotype than in carriers of the G/A and A/A genotypes of the -308G/A polymorphism ( P = 0.022 and P = 0.043, respectively). Conclusions Our results suggest that the G/G genotype of the TNF-α -308G/A polymorphism increases insulin levels and insulin resistance in women with GDM and that the AG haplotype is a genetic risk factor for GDM in our study population.

The Lacandones are considered descendants of the Maya Civilization that found refuge in the jungle during the Spanish colonization. They were able to live in absolute isolation until 1990 when an acculturation process began. This is a cross-sectional study that included 46.7% of the total Lacandon population. Weight, height, overnight fasting plasma glucose, urea, creatinine, uric acid, hemoglobin, triglycerides and HDL-cholesterol levels were determined. BMI and age have a positive correlation for subjects younger than 40 years (r = 0.51). Diabetes prevalence is 1.1%, and all cases are in the most acculturated town (Palenque). Prediabetes prevalence is 5.85% and all the cases have also hypertriglyceridemia. 19% of the prediabetes cases are between 10 and 19 years old. Hypercholesterolemia and hypertriglyceridemia prevalences are 20.7% and 45.1% respectively and there are cases in all the age groups. The study showed the need to implement public health programs to revert the obesity tendency in the young Lacandon population to avoid in long term the burden of non-communicable diseases that would affect most of their productive life.

The aim of this study was to investigate the association of the rs2240308 and rs1133683 polymorphisms in the AXIN2 gene with colorectal cancer (CRC) in Mexican patients.Genomic DNAs from 201 CRC patients and 100 healthy blood donors were analyzed for AXIN2 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Statistical associations were calculated using the odds ratio (OR) test.The genotype distribution of the rs1133683 polymorphism C T showed a statistical difference between the two study groups (p = 0.0019). Moreover, OR analyses demonstrated that individuals with either the C/T or T/T genotype have a decreased risk for CRC compared with individuals with the C/C genotype (OR = 0.47, 95% confidence interval [CI] = 0.25-0.86, p = 0.0134 and OR = 0.24, 95% CI = 0.10-0.57, p = 0.005, respectively). This association was also evident in a stratified analysis based on tumor-node-metastasis (TNM) stage. For the rs2240308 polymorphism C T, the OR analysis showed a significantly increased risk for carriers of the T/T genotype (OR = 2.64, 95% CI = 1.12-6.24, p = 0.0236) and this association was also evident in the stratified analysis by TNM stage.Our results indicate the possibility that variations in the AXIN2 gene may play a significant role in promoting or preventing CRC development.

Objectives To determine whether the well-known genetic structure of the Mexican population observed with other multiallelic markers can be detected by analyzing functional polymorphisms of cytokine and other inflammatory-response-related genes. Methods A total of 834 Mestizo individuals from five Mexican cities and 92 Lacandonians – an Amerindian group from southeastern Mexico – were genotyped for 14 polymorphisms in the CRP, IL10, IL6, TGFB1, TNFA, LTA, ICAM1 IFNG, and IL1RN genes. Allele and haplotype frequencies were used for genetic structure analysis using F–statistics pairwise distances and multidimensional scaling plot. Ancestry analysis was performed, as well. Results Significant interpopulational differences at the allele and haplotype frequency level were observed, mainly between Northern (Guadalajara, Monterrey, and Culiacan) and Southern (Tierra Blanca and Puebla) Mexican populations. Also, low but significant substructure was detected between some populations from these two broad regions. Interestingly, both Lacandonian populations were highly differentiated from each other and with respect to Mestizos. Consistent with previous data, Amerindian ancestry in the Southern Mexican groups was higher compared to Northern ones. Conclusions The Mexican population exhibits regional differences in functional polymorphisms of inflammatory-response genes, as observed for other genetic markers. This information constitutes a reference for epidemiological studies that include these genetic markers to assess the susceptibility of the Mexican population to several immune-response-related diseases, such as diabetes, obesity, and renal disease, which have been shown to be common in the Mexican population but with prevalence differences within this country.

Overweight and obesity are considered complex entities in which there are alterations in the concentration of antioxidant enzymes. It has been reported that glutathione peroxidase 3 (GPx3), an extracellular enzyme involved in the reduction of both hydro- and lipoperoxides, shows changes both in gene expression and protein concentration in animal models for type 2 diabetes (T2D) and obesity, but the variability of GPx3 levels in different human populations and under different health conditions are currently unclear. We undertook this study to determine the GPx3 levels in overweight and obese subjects from central Mexico.Biochemical profile (serum glucose, insulin and lipid profile) and GPx3 concentrations were determined in 28 healthy subjects (control) and 133 subjects who were overweight or obese (OW-OB).The OW-OB group had a higher concentration of triacylglycerides (TAG) compared with the control group (201.2 ± 88.7 vs. 100.3 ± 46.4 mg/dL, p0.05) and the TAG/high density lipoprotein-cholesterol (HDL-C) index (5.6 ± 2.8 vs. 2.1 ± 1.2, p0.05), whereas the concentration of HDL-C decreased (38.2 ± 8.7 vs. 50.1 ± 14.5 mg/dL, p0.05). Serum GPx3 was significantly higher in the OW-OB group than in the control group (175.4 ± 25.4 vs. 143.5 ± 23.1 ng/dL). GPx3 concentration correlated with insulin sensitivity (IS) and the TAG/HDL-C index (Rho = -0.2336 and Rho = 0.2275) (p0.01).The TAG/HDL-C index and serum GPx3 concentration increased in the OW-OB group. In addition, GPx3 had a significant correlation with IS, weight, and the TAG/HDL-C index.

OBJECTIVES The study's objective was to assess the association between the PRSS1 R122H and N29I and the SPINK1 N34S mutations and acute pancreatitis (AP) and recurrent pancreatitis in Mexican pediatric patients. METHODS The N34S and R122H mutations were detected using polymerase chain reaction-restriction fragment length polymorphism, and the N29I mutation was detected using allele-specific polymerase chain reaction in 92 pancreatitis patients (58 AP and 34 recurrent pancreatitis patients) and 144 controls. RESULTS We found 1 mutated allele in 4 (4.3%) of 92 pancreatitis patients and none in the controls. All 4 patients bearing mutations had AP, with a frequency of 6.8% (4/58). Three (5.2%) of 58 patients were heterozygous for the N34S mutation, and 1 (1.7%) of 58 patients was heterozygous for the N29I mutation. The comparison between the AP and control groups revealed both a significant number of patients carrying any mutations in the screened genes (P = 0.008) and bearing the N34S mutation (P = 0.023). Moreover, we found that the N34S G allele increased the risk of developing AP (odds ratio, 10.3; confidence interval, 1.1-248.8). CONCLUSIONS Patients bearing the N34S G allele exhibited a 10-fold increased risk of developing AP compared with controls, suggesting that the SPINK1 N34S mutation represents an etiologic risk factor for AP in our Mexican pediatric patients.

Objective: We undertook this study to determine the relationship among -174G>C and 598G>A polymorphisms in the promoter region of interleukin-6, obesity, and metabolic abnormalities in subjects from central Mexico. Methods: Included in the study were 150 subjects who were not first-degree relatives of patients with diabetes and 106 blood samples from the general population. All were genotyped using polymerase chain reaction (PCR) restriction fragment-length polymorphism. Logistic regression analysis was used to assess the relationships among haplotypes, obesity, and metabolic abnormalities. Results: Only 2 haplotypes were observed: the -174G -598G and -174C -598A (D'=1.00). The -174G -598G-haplotype was associated with type 2 diabetes (OR 3.35, 95%, CI 1.16-9.71). The relationship of obesity with insulin insensitivity and obesity with hyperinsulinemia was modified by the presence of this haplotype (from OR 10.07, 95% CI 3.86-23.30 to OR 12.20, 95% CI 4.40-33.85 and OR 6.70, 95% CI 2.02-22.23 to OR 8.08, 95% CI 2.28-28.62, respectively). Conclusions: In the Mexican population, interleukin-6 haplotypes are associated with diabetes, suggesting that their contribution may be by means of modifying the relationship between obesity and metabolic abnormalities.

Background and Aims Obesity correlates with a chronic and low-grade inflammation status. C-reactive protein (CRP) measurement has been used as an independent risk marker for future cardiovascular events. CRP level shows interindividual variability due to environmental and genetic factors. The aim of this study was to assess the association of functional polymorphisms on CRP , IL6 , and TNFA genes with serum CRP levels in Mexican mestizo adolescents. Methods Body mass index (BMI), serum high-sensitivity C-reactive protein (hsCRP) levels, and genotypes for CRP +1444C>T, IL6 –174G>C, and TNFA –308G>A polymorphisms were obtained from 418 unrelated Mexican adolescents. Genetic association with hsCRP levels was evaluated by means of a dominant genetic model with uni- and multivariate analysis. Results Genotype frequencies for all three polymorphisms were according to Hardy-Weinberg equilibrium (HWE). CRP +1444T, TNFA –308A, and IL6 –174C allele frequencies were 37, 7, and 10%, respectively. CRP +1444T was associated with higher mean CRP levels independent of age, gender and BMI (β = 0.21; 95% confidence interval [95% CI] = 0.02–0.39); p = 0.030). IL6 –174C was associated with low CRP levels in the overweight group ( p = 0.005). IL6 –174G>C and TNFA –308G>A allele frequencies observed from this Mexican sample were similar to data for other Mexican populations. Conclusions The CRP +1444C>T polymorphism was associated with CRP levels in Mexican adolescents and could be used as a genetic marker for the early detection of individuals at risk for developing obesity-related conditions such as cardiovascular disease or type 2 diabetes mellitus in early adulthood.

Background/Aims: It has been proposed that preeclampsia is a metabolic syndrome of pregnancy. The polymorphisms PstI and MaeIII of INS, NsiI of INSR and Ala513Pro and Gly972Arg of IRS1 have been associated with metabolic syndrome; moreover, the products of these genes are functionally contiguous during insulin signaling. The aim of this study was to assess whether these polymorphisms are associated with preeclampsia. Methods: 46 normotensive pregnant women and 43 preeclamptic patients were included in the study to develop a clinical, biochemical and genotypic profile of preeclampsia. Clinical evaluation consisted of measurement of blood pressure, height and weight. Peripheral blood samples were collected for determination of fasting glucose and insulin concentrations and for extraction of genomic DNA. Proteinuria was determined. Polymorphisms were detected using PCR-RFLP. Results: The normotensive and preeclampsia groups did not differ significantly in clinical and biochemical traits, except for systolic and diastolic blood pressure (p < 0.0001). Polymorphisms previously associated with metabolic syndrome in Mexican populations were not associated with preeclampsia in Mexican women (p > 0.05). Conclusion: The lack of an association between preeclampsia and the polymorphisms studied suggests that other genes whose products do not have direct functional interaction with metabolic syndrome or epigenetic factors may play a role in preeclampsia.

Cardiovascular (CV) risk factors are influenced by behavioral, cultural, and social factors, suggesting that acculturation plays a significant role in the emergency and growth of chronic disease. The objective of this study was to determine the relation between CV risk factors and the main components of acculturation, in Yaquis and Tepehuanos Indians from Mexico.This was a cross-sectional population-based study in Yaquis and Tepehuanos communities from the Yaqui Valley in Sonora and the Sierra Madre Occidental Mountains in Durango, in northwest Mexico. Acculturation status is different in both ethnic groups, with Tepehuanos living in small and remote communities retaining their traditional lifestyle and Yaquis living in well-communicated communities that have assumed Westernized lifestyles.A total of 278 indigenous (120 Tepehuanos and 158 Yaquis) were randomly enrolled. Prevalence of obesity (48.1 and 6.7%, p0.001), diabetes (18.3 and 0.83%, p0.001), hypertriglyceridemia (43.0 and 15.0%, p0.001), alcohol consumption (46.8 and 26.6%, p0.001), and smoking (29.7 and 15.0%, p = 0.006) were significantly higher in Yaquis Indians. High blood pressure (6.3 and 3.3%, p = 0.40) and low HDL-cholesterol (42.4 and 34.2%, p = 0.22) were similar between Yaquis and Tepehuanos. Multivariate regression analysis adjusted by sex and age showed a significant association between calorie intake from saturated fat, but not other nutrients of customary diet, with hyperglycemia (OR 7.4, 95% CI 2.6-20.1), hypertriglyceridemia (OR 3.1, 95% CI 1.5-6.3), and obesity (OR 3.4, 95% CI 1.6-10.1).Among the components of acculturation, intake of saturated fat is the most strongly associated with the development of CV risk factors.

Objectives To describe the clinical picture and outcome, and to assess the etiological factors of acute and recurrent pancreatitis in children. Methods Thirty-six (65.5%) patients with acute and 19 (34.5%) with recurrent pancreatitis were studied. Mean age was 126 (41.3 SD) months; 27 (49.1%) were females. Setting A pediatric referral hospital. Period 2000-2005. Design Cross-sectional. Variables Clinical and laboratory data and etiological factors. Statistics Chi2-test, Fisher test, OR, confidence interval, Student t-test and Mann-Whitney U-test. Results The most frequent symptom in acute and recurrent pancreatitis was abdominal pain, followed by vomiting and ileus. The severity of pancreatitis and complications were similar in both groups. Biliary stones, family history of pancreatitis, drug ingestion and hypercalcemia occurred in both groups. Abdominal trauma and acute hepatitis A occurred in patients with acute pancreatitis; triglyceride>5.65 mmol/L, pancreas divisum and DeltaF508 mutation occurred in patients with recurrent pancreatitis. No difference was observed when frequency factors between study groups were compared. Conclusions The clinical picture and etiological factors were similar in both groups. Since one out of every three children with acute pancreatitis in this series presented recurrences, it was not considered to be a 'benign disease'. Fifteen different etiological factors were identified in two-thirds of the cases.

Asthma is an inflammatory airway disease characterized by increased serum IgE levels, mucus hypersecretion and infiltration of inflammatory cells, and is a multifactorial disease that exhibits genetic heterogeneity. Polymorphisms in the interleukin-4 (C-590T), interleukin-4 receptor (ile50val and gln576arg), and interleukin-13 (arg130gln) genes have been described as susceptibility alleles for asthma. This study was designed to determine whether asthma susceptibility is influenced by genotypic and allelic distribution of the above polymorphisms in three Mexican subpopulations. Four hundred and thirty-seven subjects from three Mexican subpopulations were classified into two groups: general population and affected/unaffected and genotyped for the above polymorphisms. We compared the distributions of the loci in the groups. In addition, we undertook association analysis between these loci and asthma phenotype in each affected/unaffected group, and determined Nei's genetic distance between the three subpopulations. The allelic and genotypic distributions of the polymorphisms differed between the three subpopulations. There was no association between any of the polymorphisms and asthma phenotype. However, there was a differential distribution of haplogroups (P < 0.0001) between the affected and the unaffected groups from the subpopulations of Jalisco and Guerrero. The genetic distribution of the four polymorphisms in the subpopulations did not influence susceptibility to asthma. Furthermore, the difference in the prevalence of asthma in these subpopulations is not attributable to the genetic background for the four polymorphisms analysed. However, haplogroup analysis suggests that the interaction of the polymorphisms and other predisposing alleles leads to the expression of the clinical phenotype.

Aims. KiSS1is a metastasis suppressor gene associated with inhibition of cellular chemotaxis and invasion attenuating the metastasis in melanoma and breast cancer cell lines. Along theKiSS-1gene at least 294 SNPs have been described; however the association of these polymorphisms as genetic markers for metastasis in breast cancer studies has not been investigated. Here we describe two simple PCR-RFLPs protocols to identify the rs5780218 (9DelT) and the rs12998 (E20K)KiSS1polymorphisms and the allelic, genotypic, and haplotypic frequencies in Mexican general population (GP) and patients with benign breast disease (BBD) or breast cancer (BC).Results.The rs5780218 polymorphism was individually associated with breast cancer(P=0.0332)and the rs12998 polymorphism shows statistically significant differences when GP versus case (BC and BBD) groups were compared(P<0.0001). The H1 Haplotype (G/-) occurred more frequently in BC group (0.4256) whereas H2 haplotype (G/T) was the most prevalent in BBD group (0.4674).Conclusions.Our data indicated that the rs5780218 polymorphism individually confers susceptibility for development of breast cancer in Mexican population and a possible role as a genetic marker in breast cancer metastasis for H1 haplotype (Wt/variant) inKiSS1gene must be analyzed in other populations.

The etiology of preeclampsia is still a matter of controversy. An association between hyperhomocysteinemia and preeclamptic patients has been described. A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased plasma homocysteine concentrations. In addition, the polymorphism of gene encoding for Factor V Leiden G1691A is associated with a prothrombotic state in heterozygous subjects. Both mutations in these thrombophilic proteins appear to have different prevalence in the general population and in patients with preeclampsia/eclampsia (PE/E). We studied single nucleotide polymorphisms for MTHFR C677T and coagulation Factor V Leiden in 33 Mexican patients with PE/E as a genetic risk factor for these diseases, comparing with a normotensive pregnant control group. The genotype and allele frequencies of MTHFR C677T and Factor V Leiden mutations between Mexican women with PE/E and healthy controls were not different. We conclude that these polymorphisms do not contribute in the etiology of PE/E as it has been reported in other populations.

Polymorphisms of leptin receptor (LEPR) may contribute to a common form of obesity and, as a consequence, obesity-related diseases. We evaluated the potential role of genetic variation at the LEPR gene in heart sympathetic activity and other traits related to obesity in Mexican adolescents. Adolescents aged between 12 and 17 years, with steady body weight for the last 3 months were included. We evaluated anthropometric measurements, blood pressure, seric glucose, insulin, leptin levels, heart sympathetic activity (by electrocardiograph monitoring at rest), and the Gln223Arg and Pro1019Pro LEPR polymorphisms in each subject. In total, 103 adolescents (55 obese and 48 nonobese) were included. The group of obese adolescents showed higher sympathetic activity, blood pressure, glucose, insulin, and leptin levels. The genotype frequencies for the two polymorphisms were found to be in Hardy-Weinberg equilibrium. There was no difference in the genotype frequencies for Gln223Arg or Pro1019Pro polymorphisms between obese and nonobese adolescents. However, there was a higher prevalence of Gln223 allele among subjects with higher insulin levels (0.72 vs 0.57; P = 0.04 for adolescents with insulin levels higher and lower than 100 pmol/l, respectively). According to Gln223Arg polymorphism, those with Gln allele (Gln/Gln and Gln/Arg) had higher heart sympathetic activity, body fat percentage, and leptin levels. To conclude, our results support the hypothesis that Gln223Arg polymorphism of LEPR in Mexican adolescents is associated with haemodynamic and metabolic disturbances related to obesity.

Type 2 diabetes mellitus is a complex metabolic disorder resulting from the action and interaction of many genetic and environmental factors. It has been reported that polymorphisms in genes involved in the metabolism of glucose are associated with the susceptibility to develop type 2 diabetes mellitus. Although the risk of developing type 2 diabetes mellitus increases with age, as well as with obesity and hypertension, its prevalence and incidence are different among geographical regions and ethnic groups. In Mexico, a higher prevalence and incidence has been described in the south of the country, and differences between urban and rural communities have been observed.We studied 73 individuals from Santiago Jamiltepec, a small indigenous community from Oaxaca State, Mexico. This population has shown a high prevalence of type 2 diabetes mellitus, and the aim of this study was to analyze the relationship between the Pst I (insulin gene), Nsi I (insulin receptor gene) and Gly972Arg (insulin receptor substrate 1 gene) polymorphisms and type 2 diabetes mellitus, obesity and hypertension in this population. Clinical evaluation consisted of BMI and blood pressure measurements, and biochemical assays consisted of determination of fasting plasma insulin and glucose levels. PCR and restriction enzyme digestion analysis were applied to genomic DNA to identify the three polymorphisms. From statistical analysis carried out here, individually, the Pst I, Nsi I and Gly972Arg polymorphisms were not associated with the type 2 diabetes, obese or hypertensive phenotypes in this population. Nevertheless, there was an association between the Nsi I and Pst I polymorphisms and increased serum insulin levels.

This study compares the detection of Mycobacterium tuberculosis through bacilloscopy (Ziehl-Neelsen stain), growth in Lowenstein-Jensen medium, and polymerase chain reaction (PCR) carried out with DNA taken directly from various types of samples. A total of 252 samples were analyzed (114 sputum, 96 urine, 15 cerebrospinal fluid, and 27 of other types) from 160 patients with any form of suspected tuberculosis who came to the Clinical Pathology Laboratory of the Specialties Hospital of the Western National Medical Center of the Mexican Social Security Institute. In all cases Ziehl-Neelsen stains were done, as were also cultures with Lowenstein-Jensen medium and PCR amplification of a segment of 285 base pairs specific to the M. tuberculosis complex. Of the 252 samples, with the culture, 18 were positive for nontuberculous mycobacteria. Of the 234 others, 12 (5.1%) were positive with the PCR and the culture, 174 (74.4%) negative in both tests, 47 (20.1%) positive with the PCR and negative with the culture, and 1 (0.4%) negative with the PCR and positive with the culture. Using the culture as the reference test, the PCR provided a sensitivity of 92.3%, a specificity of 78.7%, a positive predictive value of 20.3%, and a negative predictive value of 99.4%. The PCR detection limit with DNA taken from culture was 10 fg, equivalent to four or five mycobacteria. Also in comparison with the culture, the PCR correctly identified the totality of the mycobacteria of the M. tuberculosis complex. Taking the culture as the reference test, when analyzing just the sputum samples, the direct PCR provided a sensitivity of 90.9%, a specificity of 89.5%, a positive predictive value of 52.6%, and a negative predictive value of 98.7%. The PCR is a sensitive and specific technique for detecting the M. tuberculosis complex in both positive and negative bacilloscopy samples. A controlled PCR procedure makes it possible to establish or to exclude the diagnosis of tuberculosis in a time that is reduced from more than three weeks to just 24 to 48 hours. This is particularly useful when an early diagnosis is needed to establish a patient's prognosis or in organ transplant cases.

Background and Aims Glutathione peroxidase 3 (GPx3) plays a main role in removing hydro- and lipoperoxides from the body. Changes in concentration and several single-nucleotide polymorphisms (SNP) at the GPX3 gene have been associated with vascular diseases, but the relationship of GPx3 with metabolic syndrome (MetS) remains unexplored. We undertook this study to determine the association of GPx3 serum levels and several GPX3 SNPs with the presence of MetS in Mexican subjects. Methods Clinical, biochemical, and anthropometric evaluation were conducted in 426 subjects assigned to three groups: control ( n = 42); risk group (RG, n = 200), and MetS group ( n = 184). Insulin sensitivity (IS) and cardiovascular risk were determined by the QUICKI and TG/HDL-C index, respectively. Serum GPx3 was determined by enzyme immunoassay and polymorphisms within GPX3 gene were identified by nucleotide sequencing. Results MetS group showed low IS and increased cardiovascular risk with respect to controls as well as higher GPx3 serum levels (172.9 ± 32.2 vs. 145.6 ± 24.8 ng/dL; p GPX3 SNPs screened were polymorphic with two haplotypes observed (CCT and TTA–rs8177404, rs8177406, and rs8177409), indicating tight linkage disequilibrium in this genetic region. No differences for either genotype or allele frequencies among groups were observed, but rs8177409 (allele T) was associated with cardiovascular risk (odds ratio [OR], 4.5; p = 0.0125). Conclusion This study shows that serum levels of GPx3 are increased in subjects with MetS and that rs8177409 SNP was associated with cardiovascular risk in a Mexican population.

Polycystic ovary syndrome is a complex and heterogeneous disease involving both reproductive and metabolic problems. It has been suggested a genetic predisposition in the etiology of this syndrome. The identification of calpain-10 gene (CAPN10) as the first candidate gene for type 2 diabetes mellitus, has focused the interest in investigating their possible relation with the polycystic ovary syndrome, because this syndrome is associated with hyperinsulinemia and insulin resistance, two metabolic abnormalities associated with type 2 diabetes mellitus.To investigate if there is association between the SNP-63 and the variant indel-19 of the CAPN10 gene and polycystic ovary syndrome in women of reproductive age.This study included 101 women (55 with polycystic ovary syndrome and 46 without polycystic ovary syndrome). The genetic variant indel-19 was identified by electrophoresis of the amplified fragments by PCR, and the SNP-63 by PCR-RFLP.The allele and genotype frequencies of the two variants do not differ significatly between women with polycystic ovary syndrome and control women group. The haplotype 21 (defined by the insertion allele of indel-19 variant and C allele of SNP-63) was found with higher frequency in both study groups, being more frequent in the polycystic ovary syndrome patients group, however, this difference was not statistically significant (p = 0.8353).The results suggest that SNP-63 and indel-19 variant of the CAPN10 gene do not represent a risk factor for polycystic ovary syndrome in our patients group.

Antiepileptic drugs (AEDs) are used for the seizures control in patients with epilepsy, however 20-30% of epileptic patients are drug resistant. Several factors contributing to the variability of the AEDs response, and this variability can be partially attributed to the presence of sequence variations (polymorphisms) in genes encoding enzymes involved in the AEDs metabolism.To describe the polymorphisms in genes that encoding for proteins involved in the metabolism of some of the major AEDs, focusing on enzymes cytochrome P450 (CYP450).There are some polymorphisms in genes encoding proteins involved in drug metabolism, particularly enzymes of superfamily CYP450, that are already considered of clinical utility in the therapeutic management. These genetic variants contribute to the variability of the activity of metabolizing enzymes, which in turn influencing the poor or inadequate therapeutic response, as well as in the occurrence of adverse effects.The identification of interindividual variability in the response to AEDs may allow the personalized treatment with the aim of maximize the efficiency and minimize risk, regardless of the clinical variability and adverse effects could be manifest in a minority of the patients.Farmacogenetica y metabolismo de farmacos antiepilepticos: implicacion de variantes geneticas en citocromos P450.Introduccion. Los farmacos antiepilepticos (FAE) son la base para el control de las crisis en pacientes con epilepsia; sin embargo, se conoce que el 20-30% de los pacientes son farmacorresistentes. Son diversos los factores que contribuyen a la variabilidad de la respuesta a los FAE, y esta variabilidad puede atribuirse, al menos en parte, a la presencia de polimorfismos (variaciones de la secuencia) en genes que codifican para enzimas involucradas en el metabolismo de los FAE. Objetivo. Describir las variaciones de la secuencia en genes que codifican para proteinas implicadas en el metabolismo de algunos de los principales FAE, con enfasis en las enzimas citocromo P450 (CYP450). Desarrollo. Existen algunos polimorfismos en genes que codifican para proteinas involucradas en el metabolismo de farmacos, particularmente enzimas de la superfamilia CYP450, que se consideran ya de utilidad clinica en el manejo terapeutico. La presencia de estas variantes geneticas contribuye a la variabilidad de la actividad de enzimas metabolizadoras, lo que, a su vez, influye en la pobre o inadecuada respuesta terapeutica, e incluso en la aparicion de efectos adversos. Conclusiones. La identificacion de la variabilidad interindividual en la respuesta a los diversos FAE puede permitir la individualizacion del tratamiento con la intencion de maximizar su eficacia y minimizar el riesgo, independientemente de que la variabilidad clinica y los efectos adversos se presenten en una minoria de pacientes.

The association between some Tumor necrosis factor-alpha (TNF-α) promoter polymorphisms and Type 2 diabetes mellitus (T2DM) remains controversial. Ethnic differences may play a role in these conflicting results. The aim of this study was to investigate the association between −308G/A and −238G/A polymorphisms located in the promoter region of the TNF-αgene and T2DM in Mexican mestizo patients. Nine hundred four individuals (259 patients with T2DM and 645 controls) were genotyped for the −308G/A and −238G/A polymorphisms by PCR—RFLP. We found that the −238A allele increased the risk of developing T2DM in Mexican patients (OR = 1.57, 95% CI: 1.07–2.29;p= 0.018). Moreover, we found that the frequency of the GA haplotype (created by the −308G and −238A alleles) was significantly increased in patients with T2DM when compared with controls (OR = 1.56, 95% CI: 1.05–2.31;p= 0.026). Our results suggest that the −238G/A polymorphism and a specific haplotype (GA) are genetic risk factors for the development of T2DM in Mexican population.

Background Type 2 of diabetes is the most common metabolic disorder and results from the interaction between genetic and environmental factors. Insulin receptor substrate-2 (IRS-2), one of the major substrates of the insulin receptor, has a crucial role in insulin signalling and in beta cell development and survival. While several polymorphisms have been identified in the IRS-2 gene, the association of the Gly1057Asp polymorphism with type 2 diabetes has been studied in European and Chinese populations, but the results have been inconsistent. Objectives The aim of this study was to investigate the association of Gly1057Asp polymorphism in insulin receptor substrate-2 (IRS-2) gene among patients with type 2 diabetes in well defined ethnic groups from Djerba Island in Southeastern Tunisia. Methods The studied population (172 Arabs and 100 Berbers) includes 162 patients with type 2 diabetes and 110 healthy controls. BMI was calculated for each subject. The subjects were unrelated and randomly selected Arabs and Berbers were equally distributed between controls and diabetics. The G1057D polymorphism of the IRS-2 gene was genotyped using PCR-RFLP assay. Results This case/control study indicated that frequency of the IRS-2 Gly1057Asp polymorphism was not significantly different between the healthy controls and type 2 diabetic groups, neither between healthy nor obese subjects, in both ethnic groups. Moreover, this polymorphism is present at a lower frequency in Djerbian than in neighbouring European populations. Conclusion These results strongly argue against a major role of the Gly1057Asp IRS-2 polymorphism in the pathogenesis of type 2 diabetes in Djerbian subjects.

The analysis of polymorphic markers within or closely linked to the cystic fibrosis transmembrane regulator (CFTR) gene is useful as a molecular tool for carrier detection of known and unknown mutations. To establish the association between mutations in the CFTR gene in western Mexican cystic fibrosis (CF) patients, the distribution of XV2c/KM19 haplotypes was analyzed by PCR and restriction enzyme digestion in 384 chromosomes from 74 CF patients, their unaffected parents, and normal subjects. The haplotype analysis revealed that haplotype B was present in 71.9% of CF chromosomes compared to 0% of non-CF chromosomes. The F508del and G542X mutations were strongly associated with haplotype B (96.7% and 100% of chromosomes, respectively). The haplotype distribution of the CF chromosomes carrying other CFTR mutations had a more heterogeneous background. Our results show that haplotype B is associated with CFTR mutations. Therefore, haplotype analysis is a suitable alternate strategy for screening CF patients with a heterogeneous clinical picture from populations with a high molecular heterogeneity where carrier detection programs are not available. In addition, it may be a helpful diagnostic tool for genetic counseling and carrier detection in the relatives of CF patients and in couples who are planning to have children.

It has been proposed that preeclampsia is a metabolic syndrome of pregnancy. The polymorphisms PstI and MaeIII of INS, NsiI of INSR and Ala513Pro and Gly972Arg of IRS1 have been associated with metabolic syndrome; moreover, the products of these genes are functionally contiguous during insulin signaling. The aim of this study was to assess whether these polymorphisms are associated with preeclampsia.46 normotensive pregnant women and 43 preeclamptic patients were included in the study to develop a clinical, biochemical and genotypic profile of preeclampsia. Clinical evaluation consisted of measurement of blood pressure, height and weight. Peripheral blood samples were collected for determination of fasting glucose and insulin concentrations and for extraction of genomic DNA. Proteinuria was determined. Polymorphisms were detected using PCR-RFLP.The normotensive and preeclampsia groups did not differ significantly in clinical and biochemical traits, except for systolic and diastolic blood pressure (p0.0001). Polymorphisms previously associated with metabolic syndrome in Mexican populations were not associated with preeclampsia in Mexican women (p0.05).The lack of an association between preeclampsia and the polymorphisms studied suggests that other genes whose products do not have direct functional interaction with metabolic syndrome or epigenetic factors may play a role in preeclampsia.

Background The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of enzymes catalyzing the stepwise degradation of glycosaminoglycans (GAGs), and are transmitted in an autosomal recessive manner, except for Hunter syndrome. Methods The levels of GAGs in 150 healthy subjects and 33 patients with MPS were determined, and results were expressed as milligrams of GAGs per grams of creatinine. Results We found that this ratio decreased with age during the first 15 years of life, but had a constant low rate between the ages of 17–40 years in healthy individuals. A different tendency was present in patients with MPS, because levels of GAG excretion in this group were higher (by four standard deviations up) compared with healthy individuals. The electrophoretic patterns of urinary GAGs in healthy subjects showed that the higher levels detected in urine were chondroitin sulfate (4 and 6) and a smaller quantity of dermatan sulfate, but in each MPS type its characteristic pattern was identified. Conclusions This is a simple, reproducible method suitable for routine laboratory separation, identification, and quantity of urinary GAGs and for diagnosing MPS syndromes.

Background Recurrent respiratory papillomatosis (RRP) is the most frequent benign neoplasm in childhood; it originates as a mild dysphonia and results in asphyxia. The RRP has been associated with an infection caused by human papillomavirus (HPV), mainly types 6 and 11, the latter being associated with more severe RRP. Objectives To analyze the frequency of the association of RRP with the HPV types in our juvenile population and to classify it according to severity. Design Observational descriptive trial. Materials and Methods Forty-seven samples of paraffin-embedded papillomas, from 26 female and 21 male children (age range, 2 weeks to 17 years) were analyzed. DNA was isolated and a 188–base pair fragment was amplified from a consensus sequence in the E1 open reading frame of several HPVs by polymerase chain reaction. The corresponding band was recovered and reamplified. The fragment was digested with the restriction enzyme Rsa I. The digestion products were compared with patterns of molecular weight markers for viral type identification. The patients' clinical records were reviewed, and RRP was classified as mild or aggressive. Results The presence of HPV types 6, 11, 16, 31, 33, 35, or 39 was confirmed in all the cases with different combinations. The χ 2 test showed no significant differences in clinical aggressiveness among the viral types. A logistic regression analysis demonstrated no association between clinical aggressiveness and any viral type or viral combination. Conclusion These results show that RRP is caused by infection with HPV types 6 and 11 in addition to many other types, with no relationship between HPV type and clinical severity.

The MPS-I is an autosomal recessive disorder caused by mutations in the IDUA gene that induce to a deficiency of glycosidase alpha-L-iduronidase that is required for degradation of heparan and dermatan sulfate. This disorder expresses a wide range of clinical symptoms.Kpnl (K) and VNTR (V) intragenic polymorphisms at the IDUA gene were studied in mestizo and Huichol Indian Mexican populations as well in 13 MPS-I patients. Data from Australian normal and MPS-I (2-4) individuals were also studied.Genotypes for IDUA K and V sites in Mexicans were in agreement with Hardy-Weinberg expectations, except for site K in Huichols. Individually, allele frequency distributions were different (p0.05) in the two normal groups for the V site. K-V haplotype frequency distributions (HFDs) in these two normal groups were also different as compared with normal Australians. In Mexican MPS-I patients, HFD was different (p0.05) with respect to both Mexican normal groups, and non-different when compared with normal or MPS-I Australians. This can be taken as evidence of linkage disequilibrium between K-V polymorphism and MPS-I gene mutation(s) at the IDUA region. A similar finding was reported. However, disequilibrium in Mexicans was determined by haplotypes different from those in Australia. In Mexican MPS-I patients, haplotype K2-V1 is increased and K1-V3 decreased with respect to the Mexican mestizo (p0.05), while in Australians, MPS-I patients had an increase of haplotypes K2-V2 and K1-V2 with respect to expected frequency.The similar HFD between Mexican and Australian MPS-I patients suggests a common genetic origin, that MPS-I mutations were introduced to Mexico by Spaniards, and that such mutations predate the dispersion between Mexican and Australian Caucasian ancestors. The differences in disequilibrium are explained rather by genetic drift.