title: Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico.
abstract: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Folate deficiency has been related to several conditions, including neural tube defects (NTDs) and cardiovascular diseases. Hence, MTHFR genetic variants have been studied worldwide, particularly the C677T and A1298C. We genotyped the C677T and A1298C MTHFR polymorphisms in Mexican Amerindians (MAs), from the largest sample included in a genetic study (n = 2026, from 62 ethnic groups), and in a geographically-matched Mexican Mestizo population (MEZ, n = 638). The 677T allele was most frequent in Mexican individuals, particularly in MAs. The frequency of this allele in both MAs and MEZs was clearly enriched in the South region of the country, followed by the Central East and South East regions. In contrast, the frequency of the 1298C risk allele in Mexicans was one of the lowest in the world. Both in MAs and MEZs the variants 677T and 1298C displayed opposite allele frequency gradients from southern to northern Mexico. Our findings suggest that in Mestizos the 677T allele was derived from Amerindians while the 1298C allele was a European contribution. Some subgroups showed an allele frequency distribution that highlighted their genetic diversity. Notably, the distribution of the frequency of the 677T allele was consistent with that of the high incidence of NTDs reported in MEZ.
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Contreras-Cubas
authors.affiliation: Genetic Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, SS, Mexico City, Mexico.
authors.forename: Beatríz E
authors.initials: BE
authors.lastname: Sánchez-Hernández
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Humberto
authors.initials: H
authors.lastname: García-Ortiz
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Martínez-Hernández
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Barajas-Olmos
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Cid
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Elvia C
authors.initials: EC
authors.lastname: Mendoza-Caamal
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Federico
authors.initials: F
authors.lastname: Centeno-Cruz
authors.affiliation: Genetic Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, SS, Mexico City, Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ortiz-Cruz
authors.affiliation: Physic Anthropology Direction, Instituto Nacional de Antropología e Historia, Museo Nacional de Antropología, Mexico City, Mexico.
authors.forename: José Concepción
authors.initials: JC
authors.lastname: Jiménez-López
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Emilio J
authors.initials: EJ
authors.lastname: Córdova
authors.affiliation: Physic Anthropology Direction, Instituto Nacional de Antropología e Historia, Museo Nacional de Antropología, Mexico City, Mexico.
authors.forename: Eva Gabriela
authors.initials: EG
authors.lastname: Salas-Bautista
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Saldaña-Alvarez
authors.affiliation: Computational Genomics, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fernández-López
authors.affiliation: Genetic Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, SS, Mexico City, Mexico.
authors.forename: Osvaldo M
authors.initials: OM
authors.lastname: Mutchinick
authors.affiliation: Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.
authors.forename: Lorena
authors.identifier: http://orcid.org/0000-0002-1250-1203
authors.initials: L
authors.lastname: Orozco
mesh_terms: D000483:Alleles; D005006:Ethnicity; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008800:Mexico; D009436:Neural Tube Defects / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)