ABCA1 variant rs9282541 is associated with metabolic syndrome in Maya children.

INTRODUCTION: Metabolic syndrome (MetS) is a metabolic disorder encompassing risk factors for cardiovascular disease and type 2 diabetes (T2D). In Mexico, the MetS is a national health problem in adults and children. Environmental and genetic factors condition the MetS. However, studies to elucidate the contribution of genetic factors to MetS in Mexico are scarce. A recent study showed that variant rs9282541 (A-allele) in ATP-binding cassette transporter A1 (ABCA1) was associated with T2D in the Maya population in addition to low levels of high-density lipoprotein cholesterol (HDL-C). Thus, this study aimed to determine whether the genetic variant of ABCA1 A-allele (rs9282541, NM_005502.4:c.688C > T, NP_005493.2:p.Arg230Cys) is associated with MetS and its components in Mexican Maya children. METHODS: The study was conducted in 508 children aged 9-13 from the Yucatán Peninsula. MetS was identified according to the de Ferranti criteria. Genotyping was performed using TaqMan assay by real-time PCR. Evaluation of genetic ancestry group was included. RESULTS: The frequency of MetS and overweight-obesity was 45.9% and 41.6%, respectively. The genetic variant rs9282541 was associated with low HDL-C and high glucose concentrations. Remarkably, for the first time, this study showed the association of ABCA1 rs9282541 with MetS in Maya children with an OR of 3.076 (95% CI = 1.16-8.13 p = 0.023). Finally, this study reveals a high prevalence of MetS and suggests that variant rs9282541 of the ABCA1 gene plays an important role in the developing risk of MetS in Maya children.

Whole-exome sequencing in maya indigenous families: variant in PPP1R3A is associated with type 2 diabetes.

It has been presumed that increased susceptibility in Mexicans to type 2 diabetes (T2D) is attributed to the Native American genetic ancestry. Nonetheless, it is not known if there are private genetic variants that confer susceptibility to develop T2D in our population. The Maya indigenous group has the highest proportion of Native American ancestry (98%) which makes it a representative group of the original peoples of Mexico. Thus, the aim of the present study is to identify new genetic variants associated with T2D in Maya families. Whole-exome sequencing was performed on DNA samples from Maya families with a third-generation family history of T2D only in one parental line. Four variants were identified for APOB, PPP1R3A, TPPP2, and GPR1 genes, and were further tested for association with T2D in 600 unrelated Maya in a case-control study. For the first time, rs1799999 in PPP1R3A was associated with risk of T2D in Mayan Mexican individuals (OR = 1.625, P = 0.014). Interestingly, carriers of rs1799999 presented increased values of HOMA-IR. In addition, rs1801702 in APOB was associated with total cholesterol and LDL-C (P = 0.019 and P = 0.020, respectively) in normoglycemic individuals; rs3732083 in GPR1 with HOMA-IR (P = 0.016) and rs9624 in TPPP2 with total cholesterol and triglycerides (P = 0.002 and P = 0.005, respectively) in T2D subjects. Overall, these findings support the idea that there are other genetic variants yet to be described, involved in T2D development in Maya population, being insulin resistance and lipid metabolism the main mechanisms implicated. Thus, these results can contribute to the understanding of diabetes genetic background in Mexican population.