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Mol Genet Genomics. 2017 Dec;292(6):1209-1219. doi: 10.1007/s00438-017-1340-2. Epub 2017 Jul 7.

Susceptibility background for type 2 diabetes in eleven Mexican Indigenous populations: HNF4A gene analysis.

Author information

1
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Edif. F, 2o piso, Lab. 202, Av Universidad 3000, Circuito Interior S/N, Coyoacán, Cd. Universitaria, CP 04510, Mexico City, Mexico.
2
Laboratorio de Endocrinología Molecular, Hospital Juárez de México, Av. Instituto Politécnico Nacional 5160, Gustavo A. Madero, CP 07760, Mexico City, Mexico.
3
Departamento de Trasplantes, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez, Belisario Domínguez Secc 16, CP 14080, Mexico City, Mexico.
4
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química Universidad Nacional Autónoma de México, Instituto Nacional de Medicina Genómica, Periferico Sur 4809, Tlalpan, Arenal Tepepan, CP 14610, Mexico City, Mexico.
5
Unidad de Investigación Médica en Genética Humana, Centro Médico Nacional, Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtémoc 300, Cuauhtémoc, CP 06720, Mexico City, Mexico.
6
Centro Cultural Universitario "Casa de las Diligencias", Universidad Autónoma del Estado de México, Av Benito Juárez Garcia Sur 114, Centro, CP 50000, Toluca, Mexico State, Mexico.
7
Escuela Nacional de Antropología e Historia, Instituto Nacional de Antropología e Historia, Mexico City, Mexico.
8
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Edif. F, 2o piso, Lab. 202, Av Universidad 3000, Circuito Interior S/N, Coyoacán, Cd. Universitaria, CP 04510, Mexico City, Mexico. menjivar@unam.mx.
9
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química Universidad Nacional Autónoma de México, Instituto Nacional de Medicina Genómica, Periferico Sur 4809, Tlalpan, Arenal Tepepan, CP 14610, Mexico City, Mexico. menjivar@unam.mx.

Abstract

The genetic risk of developing type 2 diabetes (T2D) increases in parallel with the proportion of Native American ancestry. Mestizo Mexicans have a 70% Native Amerindian genetic background. The T130I polymorphism in the HNF4A gene has been associated with early-onset T2D in mestizo Mexicans. Thus, the aim of the present study was to evaluate the frequency and relationship of the T130I variant in the HNF4A gene with risk factors for developing T2D in eleven indigenous groups from Mexico. In two groups, all exons of the HNF4A gene were directly sequenced; in the remaining the T130I polymorphism was analyzed by restriction fragment length polymorphism. Ancestry informative markers were assessed to confirm the Amerindian component. An additional analysis of EHH was carried out. Interestingly, HNF4A gene screening revealed only the presence of the T130I polymorphism. The range frequency of the risk allele (T) in the indigenous groups was from 2.7 to 16%. Genotypic frequencies (T130I/I130I) were higher and significantly different from those of all of the populations included in the HapMap Project (P < 0.005). EHH scores suggest a positive selection for T130I polymorphism. Metabolic traits indicate a relationship between the T130I/I130I genotypes with high triglyceride concentrations in the indigenous groups (P < 0.005). These results strongly suggest that the high frequency of the T130I polymorphism and its biological relationship with dysfunction in lipid metabolism in Mexican indigenous groups is a risk factor for the developing of T2D in Mexicans.

KEYWORDS:

Diabetes background; HNF4A gene; Mexican indigenous; T130I polymorphism

PMID:
28688048
DOI:
10.1007/s00438-017-1340-2
[Indexed for MEDLINE]

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