We investigated whether variants in major candidate genes for food intake and body weight regulation contribute to obesity‐related traits under a multilocus perspective. We studied 375 Brazilian subjects from partially isolated African‐derived populations (quilombos). Seven variants displaying conflicting results in previous reports and supposedly implicated in the susceptibility of obesity‐related phenotypes were investigated: β2‐adrenergic receptor (ADRB2) (Arg16Gly), insulin induced gene 2 (INSIG2) (rs7566605), leptin (LEP) (A19G), LEP receptor (LEPR) (Gln223Arg), perilipin (PLIN) (6209T > C), peroxisome proliferator‐activated receptor‐γ (PPARG) (Pro12Ala), and resistin (RETN) (−420C > G). Regression models as well as generalized multifactor dimensionality reduction (GMDR) were employed to test the contribution of individual effects and higher‐order interactions to BMI and waist‐hip ratio (WHR) variation and risk of overweight/obesity. The best multilocus association signal identified in the quilombos was further examined in an independent sample of 334 Brazilian subjects of European ancestry. In quilombos, only the PPARG polymorphism displayed significant individual effects (WHR variation, P = 0.028). No association was observed either with the risk of overweight/obesity (BMI ≥ 25 kg/m2), risk of obesity alone (BMI ≥ 30 kg/m2) or BMI variation. However, GMDR analyses revealed an interaction between the LEPR and ADRB2 polymorphisms (P = 0.009) as well as a third‐order effect involving the latter two variants plus INSIG2 (P = 0.034) with overweight/obesity. Assessment of the LEPR‐ADRB2 interaction in the second sample indicated a marginally significant association (P = 0.0724), which was further verified to be limited to men (P = 0.0118). Together, our findings suggest evidence for a two‐locus interaction between the LEPR Gln223Arg and ADRB2 Arg16Gly variants in the risk of overweight/obesity, and highlight further the importance of multilocus effects in the genetic component of obesity.

Background. It has been widely suggested that analyses considering multilocus effects would be crucial to characterize the relationship between gene variability and essential hypertension (EH). Objective. To test for the presence of multilocus effects between/among seven polymorphisms (six genes) on blood pressure-related traits in African-derived semi-isolated Brazilian populations (quilombos). Methods. Analyses were carried out using a family-based design in a sample of 652 participants (97 families). Seven variants were investigated: ACE (rs1799752), AGT (rs669), ADD2 (rs3755351), NOS3 (rs1799983), GNB3 (rs5441 and rs5443), and GRK4 (rs1801058). Sensitivity analyses were further performed under a case-control design with unrelated participants only. Results. None of the investigated variants were associated individually with both systolic and diastolic BP levels (SBP and DBP, respectively) or EH (as a binary outcome). Multifactor dimensionality reduction-based techniques revealed a marginal association of the combined effect of both GNB3 variants on DBP levels in a family-based design (P = 0.040), whereas a putative NOS3-GRK4 interaction also in relation to DBP levels was observed in the case-control design only (P = 0.004). Conclusion. Our results provide limited support for the hypothesis of multilocus effects between/among the studied variants on blood pressure in quilombos. Further larger studies are needed to validate our findings.

INDEL markers were useful to evidence the triple interbreeding among African, European, and Amerindian in the formation of quilombo populations. The low F(ST) values suggested gene flow among quilombos from Vale do Ribeira. Our data highlight the important role of Amerindians in the formation of quilombo populations.

At least 25 African-derived populations (quilombo remnants) are believed to exist in the Ribeira River Valley, located in the southern part of São Paulo State, Brazil. We studied four Alu polymorphic loci (APO, ACE, TPA25, and FXIIIB) in individuals belonging to six quilombo remnants in addition to individuals sampled from the city of São Paulo. The allelic frequencies observed in the quilombo remnants were similar to those previously observed in African-derived populations from Central and North America. Genetic variability indexes (Fst and Gst values) in our quilombos were higher than the reported values for the majority of other populations analyzed for the same kind of markers, but lower than the variability usually observed in Amerindian groups. The observed high degree of genetic differentiation may be due to genetic drift, especially the founder effect. Our results suggest that these populations behave genetically as semi-isolates. The degree of genetic variability within populations was larger than among them, a finding described in other studies. In the neighbor-joining tree, some of the Brazilian quilombos clustered with the African and African-derived populations (São Pedro and Galvão), others with the Europeans (Pilões, Maria Rosa, and Abobral). Pedro Cubas was placed in an isolated branch. Principal component analysis was also performed and confirmed the trends observed in the neighbor-joining tree. Overall, the quilombos showed a higher degree of gene flow than average when compared to other worldwide populations, but similar to other African-derived populations.