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The purpose of this study is to investigate the association of variant alleles (rs2781666 and rs2781667) at ARG1 to be involved in the generation of essential hypertension (EH) phenotypes in human subjects. The ARG1 noncoding polymorphisms (rs2781666; Chr6:131572419-G/T and rs2781667; Chr6:131573754-C/T) were investigated in 570 subjects, including 285 individuals diagnosed with EH. Determination of serum arginase activity and concentrations of nitric oxide catabolites were detected by the colorimetric enzymatic assay. Genetic typing of the noncoding polymorphisms, in ARG1, was performed using PCR and restriction digestion strategy. A significant increase in arginase activity was observed in individuals exhibiting EH phenotypes, compared with controls ( p < 0.0001). Arginase showed negative correlation with serum nitrite and nitrate ( r = −0.446 and r = −0.6075, respectively). A significant difference to be claimed in the distribution of SNPotypes, in rs2781666 and rs2781667, between cases and controls ( p = 0.0086 and p = 0.0232; respectively). Interestingly, variant allele T, at both loci, is tightly linked to the disease phenotypes compared to the wild-type allele ( p = 0.002; and p = 0.007, respectively). To our knowledge, this report is the first ever that described arginase activity, and the ARG1 polymorphism data of individuals originated in Pakistan, segregating EH phenotypes, thus, highlighting a novel risk factor for the disease. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms mapped in the ARG1 locus (chr6:131894344-131905472) and their functional effects on type 2 diabetes mellitus (T2DM) have not been thoroughly elucidated to date. The present study aimed to investigate an association between variant alleles at ARG1 locus and T2DM in patients. Two ARG1 single nucleotide polymorphisms (SNPs) were characterized in a representative sample of 500 patients with T2DM and 500 healthy volunteers. Serum lipid profile was studied by spectrophotometric analysis, while serum arginase-1 concentrations were determined by an enzyme-linked immunosorbent assay. The regions, encompassing target SNPs (rs2781665 and rs2781666), were amplified by polymerase chain reaction and genotypes were assigned by restriction digestions. A statistically significant increase was observed in the serum hs-CRP and arginase-1 levels in the subjects with T2DM than in controls (P <0.0001; for each). The variant genotypes of rs2781666 and rs2781665 were significantly associated with T2DM when compared with controls (P< 0.0001). Moreover, type 2 diabetic patients showed higher frequencies of T allele at rs2781666 and rs2781665 compared to the controls (OR = 1.7; 95% CI=1.31-2.13; P <0.0001, and OR = 1.9; 95% CI=1.45-2.38; P <0.0001, respectively). Haplotype T-T (chr6: 131893247-131893559) mapped at rs2781665-A/T and rs2781666-G/T displays higher frequency in the subjects when compared to the healthy ethnically-matched control samples (P <0.0001). We wish to propose, the first ever observation to our knowledge that concluding high levels of arginase-1 and the ARG1 polymorphisms are possible causes to confer/augment the risk of T2DM in subjects originates in Pakistan. [ABSTRACT FROM AUTHOR]

Interleukin-8 (IL-8) is a well-known inflammatory chemokine and suggested to be involved in the development of acne vulgaris. This study investigates IL-8 plasma levels in acne patients and healthy controls and the molecular basis for the regulation of the IL-8 gene in a Pakistani population. Patients with acne vulgaris (n = 264) and healthy individuals (n = 264) were enrolled in this investigation. Plasma IL-8 levels were determined by enzyme-linked immunosorbent assay (ELISA). The genotyping for IL-8 gene was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Our data showed a statistically significant increase in IL-8 levels from acne patients compared with healthy subjects (154.2 ± 52.1 pg/mL in patients vs. 101.6 ± 33.5 pg/mL in controls, p<0.0001). The IL-8-251T>A (rs4073) polymorphism was significantly higher in patients with acne compared with the control group (p=0.013). There was a significant difference between the T and A alleles from acne cases and controls (odds ratio OR=1.6,95 % CI= 1.16-2.19, p=0.003). Logistic-regression analysis showed that the increased IL-8 levels, and the IL-8-251T>A polymorphism were significantly associated with acne. Our data suggest that the elevated IL-8 levels and the IL-8-251T>A polymorphism may be associated with acne vulgaris in the study population. [ABSTRACT FROM AUTHOR]

A case–control and trio-families study was performed to establish a potential association between TNF-alpha gene promoter SNPs at -308 and -238, and occurrence of CAD in a Pakistani population. In the first phase, 150 patients and 150 controls were enrolled in the case–control association study. In the second phase, heritability of susceptible alleles was investigated from 88 trio-families with CAD affected offspring. Biochemical analysis of lipids and hs-CRP was carried out spectrophotometrically, while serum TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay. Genotyping of the TNF-alpha SNPs were determined by PCR-RFLP method. Elevated serum TNF-alpha and hs-CRP were observed from CAD vs. controls ( P < 0.0001; for both). The evaluation of TNF-alpha-308G>A polymorphism in case–control study revealed that the said SNP was significantly associated with the increased risk of CAD. The findings demonstrated a significant link between the TNF-alpha variant allele A at -308 and CAD ( P = 0.0035), whereas the -238 SNP was not associated with the disease. Haplotype A–G of the TNF-alpha gene at -308G>A and -238G>A showed higher frequency in the patient group compared with controls ( P < 0.05). Moreover, data showed preferential transmission of the disease susceptible allele A at TNF-alpha-308 from parent to affected offspring in a trio-family study ( P < 0.0001). The current research leads to conclusion that the TNF-alpha-308G>A polymorphism is associated with CAD in the study population. Furthermore, for the first time, we showed that the TNF-alpha-308A allele was significantly associated with the familial CAD in our high risk population. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential role of IL-1A gene variations in pathogenesis of coronary artery disease (CAD) with familial history. Materials and Methods: We investigated the IL-1A-889C>T polymorphism in 335 patients with CAD and 335 healthy individuals for case-control association analysis. In this study, we also investigated the heritability of the susceptible allele from 130 trio families with CAD-affected offspring. We performed genotyping using the polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP) method. Results: The IL-1A-889 C/T polymorphism was significantly associated with CAD in patients compared with healthy controls. The minor allele T at -889 was more prevalent in cases vs controls. The results of a transmission disequilibrium test revealed a significant association between the IL-1A-889 polymorphism and CAD. The mutant genotype CT+TT was significantly associated with high levels of high-sensitivity C-reactive protein (CRP) and other relative markers from patients with CAD. Conclusion: For the first time in the literature, to our knowledge, we demonstrate a significant association of the IL-1A-889 functional polymorphism with CAD. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The resistin gene (RETN) −420C>G and +299G>A polymorphism was investigated in a case-control study from forty complex Pakistani families with coronary artery disease (CAD) history. Heritability of the susceptible/variant alleles was investigated from parent–offspring trios in these families. Method: Resistin levels were determined from 239 individuals by enzyme-linked immunosorbent assay. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism. Results: Elevated resistin levels were observed from CAD cases vs. controls (p <0.0001). The RETN −420C>G and +299G>A polymorphism was more prevalent in cases vs. controls (p <0.0001). The transmission disequilibrium test revealed a significant association of the −420 and +299 polymorphism with CAD (χ 2 =34.4, p <0.0001 and χ 2 =31.6, p <0.0001, respectively). Conclusion: Elevated resistin, and the RETN −420C>G and +299G>A polymorphism may contribute to familial CAD. The −420 and +299 variant alleles are transmitted more frequently from parent to affected offspring. This is the first report on the association of the RETN +299G>A polymorphism with CAD. [Copyright &y& Elsevier]

Resistin (RETN), recently found to be relevant to inflammation and inflammatory disorders. We, therefore, aimed to investigate the potential role of RETN gene polymorphism in pathogenesis of acne vulgaris with familial history. We investigated the RETN-420C/G polymorphism in 180 patients with acne vulgaris and 180 healthy individuals in a case-control association analysis. In this study, we also investigated the heritability of the RETN susceptible allele from 140 trio families with acne affected offspring. The genotyping was performed by polymerase chain reaction and direct DNA sequencing. The RETN-420C/G polymorphism was significantly associated with acne in patients compared with healthy controls (P=0.014). The minor allele G at -420 was more prevalent in cases vs. controls (P=0.002). The RETN-420C/G polymorphism was significantly associated with severity of acne vulgaris in patients (P=0.0097). The results of a transmission disequilibrium test revealed a significant association between the RETN-420C/G polymorphism and acne vulgaris (P<0.001). For the first time in the literature, to our knowledge, we demonstrate a significant association of the RETN-420C/G functional polymorphism with familial acne vulgaris. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms in the human arginase-1 (ARG1) gene locus and their effects on cardiovascular disease have not been thoroughly elucidated. The aim of the present study was to investigate the association of the variant ARG1 alleles rs2781666 and rs2781667 with coronary artery disease (CAD). Methods:ARG1 rs2781666G/T and rs2781667C/T polymorphisms were characterized in a case–control study consisting of 200 complex Pakistani families with CAD history. Heritability of susceptibility/variant alleles was investigated from parent–offspring trios in these families. Determination of serum liped levels was performed spectrophotometrically, while serum arginase-1 activity and the concentrations of nitric oxide metabolites were detected by enzyme colorimetric assay. Genotyping of the two polymorphic sites in the ARG1 gene was performed using polymerase chain reaction and restriction analysis. Results: A significant increase in arginase-1 activity was observed in CAD patients compared with controls (p < 0.0001). Arginase-1 was negatively correlated with serum nitrite and nitrate (r = −0.8137 and r = −0.8444, respectively). There was a significant difference in distribution of genotypes for rs2781666 and rs2781667 polymorphisms between patients and controls (p < 0.001 for each). Similarly, the variant T allele at both loci showed a significant association with the disease compared with subjects free of CAD (p < 0.0001 for each). The transmission–disequilibrium test revealed a significant association of rs2781666 and rs2781667 polymorphisms with CAD (p < 0.0001 for each). Conclusion: This report is the first to describe arginase-1 activity and an association between ARG1 gene polymorphisms and familial CAD from Pakistan. [ABSTRACT FROM AUTHOR]