Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population.

The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression.

Ancestry, diversity, and genetics of health-related traits in African-derived communities (quilombos) from Brazil.

Brazilian quilombos are communities formed by enslaved Africans and their descendants all over the country during slavery and shortly after its abolition. Quilombos harbor a great fraction of the largely unknown genetic diversity of the African diaspora in Brazil. Thus, genetic studies in quilombos have the potential to provide important insights not only into the African roots of the Brazilian population but also into the genetic bases of complex traits and human adaptation to diverse environments. This review summarizes the main results of genetic studies performed on quilombos so far. Here, we analyzed the patterns of African, Amerindian, European, and subcontinental ancestry (within Africa) of quilombos from the five different geographic regions of Brazil. In addition, uniparental markers (from the mtDNA and the Y chromosome) studies are analyzed together to reveal demographic processes and sex-biased admixture that occurred during the formation of these unique populations. Lastly, the prevalence of known malaria-adaptive African mutations and other African-specific variants discovered in quilombos, as well as the genetic bases of health-related traits, are discussed here, together with their implication for the health of populations of African descent.