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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 We found important and unpublished associations between these obesity-related genes and BC risk.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.

Interleukin-18 (IL-18) is a key cytokine responsible for immune response and involved in the process of cancer development. In this case-control study, we tested whether IL-18 promoter polymorphism contributes to breast cancer susceptibility in Brazilian patients. The two groups studied were 154 patients with breast cancer and 118 healthy individuals. The frequency of IL-18 promoter single nucleotide polymorphisms (SNPs) at positions -607 (C/A) (rs1946518) and -137 (G/C) (rs187238) was determined by polymerase chain reaction analyses. The polymorphisms genotyped in this study showed a significant association with breast cancer under different genetic models. Both SNPs showed a positive association. For the IL18-607 polymorphism the best model was the codominant genetic model [CC vs AA, P = 0.004, odds ratio (OR) = 2.782, 95% confidence interval (CI) 1.385-5.589]. For IL18-137 statistical significance was found using the recessive genetic model (P = 0.008, OR = 3.896, 95% CI 1.427-10.639). The association between the haplotypes of the IL18 gene and breast cancer was further confirmed. Our results suggest that IL18-607 and IL18-137 polymorphism contributes to increase the breast cancer risk. To our knowledge, this is the first report regarding Brazilian breast cancer patients and IL18 promoter polymorphisms.

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.

There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

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*NS U ), 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.

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Background Estrogens have a modulatory effect on several immune responses, many of which are correlated to autoimmune diseases. Estrogens act through binding to their receptors, and an overexpression of these receptors has been identified in patients with different autoimmune diseases. Here we analyzed the association of a putative functional genetic variant in the main estrogen receptor (ERα) gene ( ESR1), and the susceptibility to clinical findings and severity of SLE. Methods A total of 426 individuals (266 healthy controls and 160 SLE patients) were genotyped for the polymorphism rs2234693 in the ESR1 gene. Allele and genotype frequencies were calculated and analyzed between cases and controls using Unphased software. Results The SNP rs2234693 was not associated with SLE per se but the minor allele rs2234693-C was correlated with the presence of nephritis and discoid skin rash. On the other hand, the rs2234693-CC genotype was correlated with the absence of arthritis as well as anti-ANA and anti-RNP autoantibodies. The comprehensive clinical analysis of these patients revealed a more severe status of the disease, characterized by a younger age of onset and higher number of organs involved when compared to European populations. Conclusions Minor allele rs2234693-C was associated with renal and cutaneous involvement, as well as the absence of arthritis, anti-ANA and anti-RNP autoantibodies.