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Several genes have been associated with breast cancer (BC) susceptibility. The tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), and interferon lambda receptor 1 (IFNLR1) genes encode receptors that mediate the action of inflammatory cytokines. Previous studies have demonstrated the association of the variants rs1800693 (TNFRSF1A) and rs4649203 (IFNLR1) with some inflammatory diseases. The present study aimed to verify a possible association of these variants with BC, its clinical pathologic features, as well as epidemiological data in a Brazilian population. A total of 243 patients and 294 individuals without history of BC were genotyped for these polymorphisms through TaqMan® SNP genotyping assays by qPCR. For the TNFRSF1A gene, no significant results were found. For IFNLR1, the AA genotype (p = 0.008) and the A allele (p = 0.02) were significantly associated with a lower risk of developing BC. When analyzing the age, it was observed that each increase of one year contributes to the development of BC (p

Background The interferon pathways have been commonly implicated in autoimmune disease development but the identity of the genes involved has not yet been fully clarified. Variation in genes involved in interferon pathways is expected to have a role in the etiology of these diseases. Methods The potential association of a polymorphism in the IL28RA gene, involved in these pathways, with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and disease-related phenotypes was investigated in 603 Brazilian individuals (354 well-characterized SLE and RA patients, and 249 controls). IL28RA (rs4649203) variant was genotyped by TaqMan assay. Statistical analysis was performed including both diseases and a comprehensive list of patient clinical manifestations. Results The rs4649203-G (minor) allele was associated with SLE and RA occurrence and was shown to be a risk factor for serositis and anemia among SLE patients as well as a protective factor for rheumatoid vasculitis and rheumatoid nodules in RA patients, suggesting an association with a milder form of the disease. Conclusions The IL28RA gene may contribute to SLE and RA susceptibility and to specific clinical manifestations of the diseases.

ResumoObjetivoEste estudo teve como objetivo analisar a relação entre o polimorfismo do gene PDCD1 (programmed cell death 1) (PD1.3G/A ‐ rs11568821) com características do lúpus eritematoso sistêmico (LES) e da artrite reumatoide (AR) em uma população do sul do Brasil.MétodosA técnica de PCR‐RFLP (Polymerase Chain Reaction‐Restriction Fragment Lenght Polymorphism) foi utilizada para analisar amostras de 95 pacientes com LES e 87 com AR, assim como em 128 indivíduos do grupo controle de Santa Catarina, sul do Brasil. Foi analisada a probabilidade de equilíbrio de Hardy‐Weinberg (EHW) e a odds ratio (OR), considerando um IC 95% e p ≤ 0,05.ResultadosAs frequências alélicas PD1.3A foram de 0,095 (LES), 0,115 (AR) e 0,078 (controles). Os genótipos do grupo controle estavam em EHW, enquanto aqueles dos pacientes com LES e AR não estavam. No entanto, não foi encontrada associação entre o polimorfismo PD1.3 e a suscetibilidade ao LES ou à AR, nem com dados clínicos ou epidemiológicos.ConclusãoNão foi encontrada associação significativa entre o polimorfismo PD1.3 e a susceptibilidade ao LES ou à AR nessa população do sul do Brasil.AbstractObjectiveThis study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A ‐ rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population.MethodsPolymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR‐RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy‐Weinberg Equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05.ResultsThe PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data.ConclusionThere was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

Among several autoimmune diseases, one of the main risk factors is the female gender, and much consideration has been given to the involvement of female hormones in their etiology. B-cell activating factor (BAFF) is a key factor in survival and maturation of B cells and is overexpressed in several autoimmune patients although the mechanism behind this feature is unclear. In murine models, BAFF expression could be upregulated by exogenous estrogen treatment in splenocytes; however, no evidence of this relationship was available in humans. Here, leukocytes from healthy male and female individuals were collected and cultivated in the presence or absence of estrogen or progesterone. BAFF gene expression was accessed by quantitative PCR and compared between treated and untreated group of cells. In the presence of estrogen, BAFF expression was upregulated by more than 5 times in both genders. When exposed to progesterone, the female-originated cells showed increased expression, while the cells of male origin a significant downregulation of BAFF. Our results suggest that female hormones can modulate the expression of BAFF, a key cytokine in autoimmune pathways, in human immune cells. These data might contribute to the understanding of the etiology as well as the gender bias featured by several autoimmune disorders.

The aim of this study was to estimate the diversity of 30 insertion/deletion (INDEL) markers (Investigator(®) DIPplex kit) in a sample of 519 individuals from six Brazilian states and to evaluate their applicability in forensic genetics. All INDEL markers were found to be highly polymorphic in the Brazilian population and were in Hardy-Weinberg equilibrium. To determine their forensic suitability in the Brazilian population, the markers were evaluated for discrimination power, match probability and exclusion power. The combined discrimination power (CDP), combined match power (CMP) and combined power of exclusion (CPE) were higher than 0.999999, 3.4 × 10(-13) and 0.9973, respectively. Further comparison of 29 worldwide populations revealed significant genetic differences between continental populations and a closer relationship between the Brazilian and European populations.

The application of DNA technology in forensic investigations has grown rapidly in the last 25 years and with an exponential increase of short tandem repeats (STRs) data, usually presented as allele frequencies, that may be later used as databases for forensic and population genetics purposes. Thereby, classes of molecular markers such as single nucleotide polymorphisms and insertions/deletions (InDels) have been presented as another option of genetic marker sets. These markers can be used in paternity cases, when mutations in STR polymorphisms are present, as well as in highly degraded DNA analysis. In the present study, the allele frequencies and heterozygosity (H) of a 30 InDel markers set were determined and the forensic efficacy was evaluated through estimation of discrimination power (DP), match probability, typical paternity index and power of paternity exclusion in 108 unrelated volunteers from the State of Santa Catarina (South Brazil). The observed H per locus showed a range between 0.370 and 0.574 (mean = 0.479). HLD128 was the locus with the highest DP (DP = 0.656). DP for all markers combined was greater than 99.9999999999646 % which provides satisfactory levels of information for forensic demands. Genetic comparisons (exact tests of population differentiation and pairwise genetic distances) revealed that the population of Santa Catarina State differs from Korea and USA Afro-American populations but is similar to the Portuguese, German, Polish, Spanish and Basque populations.

Objective: The aim of this study was to investigate the frequency of the LCT*-13910C>T polymorphism associated with a high expression of lactase in the small intestine during adulthood, and to infer the lactase persistence and adult-type hypolactasia phenotypes among Euro-Brazilians and Mennonites from South Brazil. Materials and Meth ods: A sequence-specific PCR method to genotype the LCT*-13910C>T polymorphism in 292 Euro-Brazilians and 151 Mennonites (a group with European ancestry and a long history of endogamy) was developed. Using an exact test of population differentiation, the genotype and allele frequency between these and other Brazilian populations were compared. Results: The frequency of -13910*T was significantly higher among the Mennonites when compared to the Euro-Brazilian cohort (0.63 vs. 0.33, p < 0.000001). Accordingly, Mennonites had a higher prevalence of the lactase persistence genotype (88.1 vs. 55.5%, p < 0.000001). The distribution of -13910*T differed between Mennonites and all other Brazilian groups (p < 0.0001). The Euro-Brazilians from Curitiba displayed differences when compared to all other Brazilian groups (p < 0.0001), even to Euro-Brazilians from a different geographic region (p = 0.0003), but were similar to those from Porto Alegre (p = 0.2). Conclusion: Differences in the -13910*T-associated lactase persistence distribution among Euro-Brazilian groups reflect the ancestry and admixture of each particular group and should be considered for adult-type hypolactasia screening.

Objective To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). Methods This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P Results The frequencies of the -607A allele in patients with RA and in controls were 0.443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). Conclusions In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

OBJETIVO: Analisar a associação dos polimorfismos do gene interleucina-18 (IL-18) com artrite reumatoide (AR) e com fatores de risco de doenças cardiovasculares (DCV). MÉTODOS: A amostra foi constituída por 97 pacientes com AR e 151 controles saudáveis. Nos primeiros, foram analisados fatores de risco de DCV, tais como níveis do colesterol, hipertensão arterial, tabagismo e fator reumatoide, bem como o nível da proteína C-reativa (CRP). O DNA foi extraído e foram analisados os polimorfismos de nucleotídeo único (SNP) nas posições -607C/A e -137G/C do gene IL-18 em ambos os grupos. O equilíbrio de Hardy-Weinberg (EHW) e o odds ratio (OR) foram realizados, considerando IC 95% e P < 0,05. RESULTADOS: As frequências do alelo -607A nos pacientes com AR e nos controles foram de 0,443 e 0,424 e do alelo -137C foram de 0,304 e 0,291, respectivamente. As frequências do genótipo estavam em EHW, exceto em controles no locus -137 (P = 0,006). Não foi encontrada associação dos polimorfismos do gene IL-18 com AR, nem com fatores de risco de DCV, incluindo o nível do colesterol e de CRP (P > 0,05). Além disso, observaram-se mais indivíduos fumantes entre pacientes com AR em comparação aos controles (OR = 1,691; P = 0,088), e os níveis de CRP eram ligeiramente mais elevados em pacientes fumantes quando comparados aos de pacientes não fumantes (OR = 2,673; P = 0,061). CONCLUSÕES: Ao analisar uma amostra de pacientes com AR no sul do Brasil, não foi encontrada associação dos polimorfismos do gene IL-18 com AR, nem com os fatores de risco de DCV. OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05. RESULTS: The frequencies of the -607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.

Breast cancer (BC) is a complex disease and obesity is a well-known risk factor for its development, especially after menopause. Several studies have shown Single Nucleotide Polymorphisms (SNPs) linked to overweight and obesity, such as: rs1121980 (T/C) and rs9939609 (A/T) in Fat Mass and Obesity Associated gene (FTO) and rs17782313 (T/C) in Melanocortin 4 Receptor gene (MC4R). Thus, we aimed to investigate the association between these obesity-related SNPs and BC risk. One hundred BC patients and 148 healthy women from Santa Catarina, Brazil entered the study. SNPs were genotyped using Taqman assays. For statistical analyses SNPStats and SPSS softwares were used. Association analyses were performed by logistic regression and were adjusted for age and Body mass index (BMI). Multiple SNPs inheritance models (log-additive, dominant, recessive, codominant) were performed to determine odds ratios (ORs), assuming 95 % confidence interval (CI) and P value = 0.05 as the significance limit. When analyzed alone, FTO rs1121980 and rs9939609 did not show significant associations with BC development, however MC4R rs17782313 showed increased risk for BC even after adjustments (P-value = 0.032). Interestingly, the interaction of FTO and MC4R polymorphisms showed a powerful association with BC. We observed a 4.59-fold increased risk for woman who have the allele combination C/T/C (FTO rs1121980/FTO rs9939609/MC4R rs17782313) (P-value = 0.0011, adjusted for age and BMI). We found important and unpublished associations between these obesity-related genes and BC risk. These associations seem to be independent of their effect on BMI, indicating a direct role of the interaction between FTO and MC4R polymorphisms in BC development.

The CC chemokine receptor 5 (CCR5) molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3%), which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2%). This allele is uncommon in Afro-Brazilians (2.0%), rare in the Guarani Amerindians (0.4%) and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7%) and R60S in the Afro-Brazilians (5.0%). A29S and L55Q present an impaired response to β-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4% and 2.7%, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T) in Guarani (1.4%) and Y68C (g.2964A > G) in Kaingang (10.3%). The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations.

A southern Brazilian isolated community of predominantly sub-Saharan African origin, with a total population of 74 individuals and high degree of inbreeding (F = 0.081) was studied. The small sizes of the breeding (35) and effective (21) populations, as well as the very small effective migration rate (4%), suggest a high probability for the occurrence of genetic drift. A sample was typed for fourteen blood genetic systems and most of these systems seem to reveal the founder effect. This evolutionary factor was probably responsible for the absence of some polymorphic alleles frequent in African populations, i.e.: ABO*B, RHD-RHCE*DCe, GPA-GPB*NS (MNSs*NS), GPA-GPB*NS U (MNSs*NSU), HBB*S, HP*2M and ESD*2. The most unusual allele frequency was that for BCHE*A, 0.27, four times higher than its highest estimated frequency and fifty times higher than that those observed in African populations. Considering the allele frequencies of the Sub-Saharan African (A) and European (E) ancestral populations, the population studied can be quantified as containing 97.33% ± 10.41 of A alleles and 2.67% ± 10.41 of E alleles.

2 Abstract The objectives of this study were to analyze the population structure and genetic variability of two communities, Costa da Lagoa (CLG) and Sao Joao do Rio Vermelho (SJRV), located on Santa Catarina Island in southern Brazil. The two populations descend from Azores Archipelago im- migrants (Portuguese), with a minor contribution of sub-Saharan Africans and Amerindians. To estimate the relative contribution of the different ethnic groups to the current gene pool of the two communities, values of admixture were obtained using the weighted least-squares method based on allelic fre- quencies of the loci ABO, RHD-RHCE, GPA-GPB (MNSs), HBB, HP, TF, CP, AK, and ACP1. The origins of the studied populations can be quantified as fol- lows: for CLG, sub-Saharan Africans (A) = 17.3%, Iberian Europeans (P) = 75.0%, and Southern Amerindians (I) = 7.7%; for SJRV, A = 48.8%, P = 44.5%, and I = 6.7%. Because haplotype frequencies of the GPA-GPB loci in SJRV were unusual, possibly as a consequence of random genetic drift, the values of admixture were recalculated after exclusion of GPA-GPB, as fol- lows: A = 28.0%; P = 53.3%, and I = 18.7%. The total diversity (HT) was esti- mated as 42.29%, of which 99.6% can be attributed to the intrapopulational variability (HS). The interpopulational genetic variation (or standard distance, DST) corresponds to 0.19%, while the gene differentiation coefficient is 0.28%, indicative of low genetic difference. These results led to the conclusion that random genetic drift may have had an important effect on the Costa da Lagoa community, while presently gene flow might be the predominant evolu- tionary factor potentially capable of changing allele frequencies in SJRV. The communities of Costa da Lagoa (CLG) and Sao Joao do Rio Vermelho (SJRV) descend from immigrants of the Azores Archipelago (Portuguese), sub