RESUMO
Genetic, epigenetic and environmental factors play an important role in the genesis of Type 2 Diabetes Mellitus (T2D). In the genetic context, one of the strategies used to investigate possible associations with diabetes is the search for Single Nucleotide Polymorphisms (SNPs), involving the comparison of alelle frequencies, the phenotypic variations and other relevant factors, such as environmental influences and lifestyle choices, Thus, the aim of this study was to find the relationship of risk variants for T2D in SNPs (rs4994) in the ADRB3 gene; (rs1799854) in the ABCC8 gene; (rs7901695 and rs12255372) in the TCF7L2 gene; and (rs8050136) in the FTO gene in a sample of the population of the municipality of Santarém (PA), Brazilian Amazon, in the northern region of Brazil. ABCC8 (rs1799854 C>T) showed a statistically significant association with T2D. Each chosen gene and SNP has been previously implicated in T2D risk according to existing scientific literature, owing to their roles in glucose regulation and body fat.
RESUMO
CCR5Δ32 and SDF1-3'A polymorphisms were investigated in a cohort of viremia controllers, without the use of therapy, along with their influence on CD4+ T lymphocytes (TLs), CD8+ TLs, and plasma viral load (VL). The samples were analyzed from 32 HIV-1-infected individuals classified as viremia controllers 1 and 2 and viremia non-controllers, from both sexes, mostly heterosexuals, paired with 300 individuals from a control group. CCR5∆32 polymorphism was identified by PCR amplification of a fragment of 189 bp for the wild-type allele and 157 bp for the allele with the ∆32 deletion. SDF1-3'A polymorphism was identified by PCR, followed by enzymatic digestion (restriction fragment length polymorphism) with the Msp I enzyme. The relative quantification of gene expression was performed by real-time PCR. The distribution of allele and genotype frequencies did not show significant differences between the groups. The gene expression of CCR5 and SDF1 was not different between the profiles of AIDS progression. There was no significant correlation between the progression markers (CD4+ TL/CD8+ TL and VL) and the CCR5∆32 polymorphism carrier status. The 3'A allele variant was associated with a marked loss of CD4+ TLs and a higher plasma VL. Neither CCR5∆32 nor SDF1-3'A was associated with viremia control or the controlling phenotype.
Assuntos
Síndrome da Imunodeficiência Adquirida , Quimiocina CXCL12 , Infecções por HIV , Receptores CCR5 , Feminino , Humanos , Masculino , Síndrome da Imunodeficiência Adquirida/genética , Biomarcadores , Brasil , Quimiocina CXCL12/genética , Progressão da Doença , Frequência do Gene , HIV-1 , Receptores CCR5/genética , ViremiaRESUMO
This study was carried out to investigate the frequency of genetic variants related to body mass index (BMI) and type 2 diabetes (T2D) and evaluating the potential impact of risk alleles on susceptibility to these disorders in six indigenous peoples from Brazilian Amazon region. The majority of Fst values for pairwise population comparisons among the indigenous groups are low or moderate. The indigenous people show high values of differentiation with Africans, Europeans and Southeast Asians and moderate values with East Asian and American populations, as expected. The allelic frequencies among indigenous indicate that the majority of associations observed with T2D in continental populations can be replicated in native Amazonians. The genetic risk scores calculated for T2D in indigenous are high and similar to those calculated for Americans and East Asians, while the estimates obtained for obesity are low, probably due to the low frequencies of the risk allele of the FTO gene found in our samples. ADRB3-rs4994 and ABCC8-rs1799854 genes showed a significant association with BMI and waist circumference, and the KCNJ11-rs5219 gene with hyperglycemia. These results emphasize the importance of knowing the genetic variability underlying complex genetic diseases in indigenous peoples and the search for particular or rare variants.