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Gene. 2018 Dec 30;679:160-171. doi: 10.1016/j.gene.2018.08.076. Epub 2018 Aug 31.

Gene variants in AKT1, GCKR and SOCS3 are differentially associated with metabolic traits in Mexican Amerindians and Mestizos.

Author information

1
Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, CDMX, Mexico; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico.
2
Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, CDMX, Mexico.
3
Clinical Area, Instituto Nacional de Medicina Genómica, SS, CDMX, Mexico.
4
Medical Research Unit in Metabolic Diseases, UMAE Hospital de Cardiología, Centro Médico Nacional Siglo XXI, IMSS, CDMX, Mexico.
5
Research Director of the General Hospital of Mexico "Dr. Eduardo Liceaga", SS, CDMX, Mexico.
6
Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, CDMX, Mexico. Electronic address: lorozco@inmegen.gob.mx.

Abstract

Amerindian ancestry appears to be a risk factor for metabolic diseases (MetD), making Mexicans an ideal population to better understand the genetic architecture of metabolic health. In this study, we determine the association of genetic variants previously reported with metabolic entities, in two Mexican populations, including the largest sample of Amerindians reported to date. We investigated the association of eigth single-nucleotide polymorphisms (SNPs) in AKT1, GCKR, and SOCS3 genes with different metabolic traits in 1923 Mexican Amerindians (MAs) belonging to 57 ethnic groups, and 855 Mestizos (MEZs). The allele frequency of 7/8 SNPs showed significant differences between MAs and MEZs. Interestingly, some alleles were monomorphic in particular ethnic groups, and highly frequent in other ones. With the exception of GCKR rs1260326T, as expected, all SNP frequencies in the MEZ population had intermediate values between its two main ancestral populations (MAs and Iberian populations in Spain [IBS]). We detected ethnic differences in linkage disequilibrium patterns and haplotype structure between MAs and MEZs, possibly due to the high genetic heterogeneity in these populations. Remarkably, AKT1 was associated with hypertension in MEZs, but not in MAs. GCKR was associated with protection against type 2 diabetes (T2D) in MAs, and with hypertriglyceridemia and protection against low HDL Cholesterol (HDL-C) levels in MEZs. The CAT haplotype in SOCS3 was associated with metabolic syndrome (MetS) in MEZs, and correlated with protection against high blood pressure (HBP) and risk for high waist circumference and T2D in MAs. Our results show differential genetic associations with metabolic traits between MAs and MEZs, possibly due to the differences in genetic structure between these Mexican populations.

KEYWORDS:

HDL-Cholesterol; Hypertension; Hypertriglyceridemia; Mestizos; Mexican Amerindians; Mexican population; Type 2 diabetes; Waist circumference

PMID:
30176313
DOI:
10.1016/j.gene.2018.08.076
[Indexed for MEDLINE]

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