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Circ Cardiovasc Genet. 2015 Aug;8(4):603-9. doi: 10.1161/CIRCGENETICS.114.000942. Epub 2015 May 28.

Functional Polymorphism rs13306560 of the MTHFR Gene Is Associated With Essential Hypertension in a Mexican-Mestizo Population.

Author information

1
From the División de Medicina Genómica (J.C.P.-R.), División de Investigación Biomédica (L.J.C.-M., B.R.-R., C.P.-F., B.L.-H.), and Subdirección de Enseñanza e Investigación (R.M.C.-V.), CMN 20 de Noviembre-ISSSTE, México, D.F., México; Departamento de Fisiología y Grupo de Estudio en Genómica y Proteómica de Enfermedades Cardiovasculares, Instituto Nacional de Cardiología "Ignacio Chávez", México, D.F., México (G.V.A., N.M.-R.); Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química-UNAM, Instituto Nacional de Medicina Genómica, México, D.F., México (S.C.-Q.); Unidad de Investigación en Obesidad, Facultad de Medicina-UNAM, Clínica de Obesidad, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F., México (P.C.); Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., México (R.E.-M., R.M.C.-V.); and Unidad de Medicina Física y Rehabilitación Centro, UMAE, Hospital de Traumatología y Ortopedia "Lomas Verdes", Instituto Mexicano del Seguro Social, México, D.F., México (D.R.-M.).
2
From the División de Medicina Genómica (J.C.P.-R.), División de Investigación Biomédica (L.J.C.-M., B.R.-R., C.P.-F., B.L.-H.), and Subdirección de Enseñanza e Investigación (R.M.C.-V.), CMN 20 de Noviembre-ISSSTE, México, D.F., México; Departamento de Fisiología y Grupo de Estudio en Genómica y Proteómica de Enfermedades Cardiovasculares, Instituto Nacional de Cardiología "Ignacio Chávez", México, D.F., México (G.V.A., N.M.-R.); Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química-UNAM, Instituto Nacional de Medicina Genómica, México, D.F., México (S.C.-Q.); Unidad de Investigación en Obesidad, Facultad de Medicina-UNAM, Clínica de Obesidad, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F., México (P.C.); Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., México (R.E.-M., R.M.C.-V.); and Unidad de Medicina Física y Rehabilitación Centro, UMAE, Hospital de Traumatología y Ortopedia "Lomas Verdes", Instituto Mexicano del Seguro Social, México, D.F., México (D.R.-M.). rmcoralv@gmail.com rcoral@ipn.mx.

Abstract

BACKGROUND:

Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been associated with diastolic blood pressure, hypertension, and other cardiovascular diseases; however, results of these studies are still controversial. In this study, we sought to determine whether 2 functional variants (rs1801133 and rs13306560) within the MTHFR are associated with hypertension in Mexican-Mestizos.

METHODS AND RESULTS:

We performed a case-control study with 1214 subjects including adults and children to test for the association of both single nucleotide polymorphisms with essential hypertension. The adult group included 764 participants (372 patients and 391 controls) and the group of children included 418 participants (209 patients and 209 controls). rs13306560 was associated with essential hypertension in adults (odds ratio, 4.281; 95% confidence interval, 1.841-9.955; P=0.0003) with a statistical power >0.8. In children, none of the polymorphisms was associated with essential hypertension. In addition, we assessed the effect of the rs13306560 polymorphism on the MTHFR promoter region by means of luciferase reporter gene assays using human umbilical vein endothelial cells. Cells transfected with the pMTHFRaLUC construct showed an ≈25% reduction in luciferase activity (P=0.003). Furthermore, the promoter activity was reduced considerably by in vitro methylation of CpG sequences.

CONCLUSIONS:

Our data suggest that the rs13306560 polymorphism of the MTHFR may be part of the observed hypertension process in Mexican-Mestizo populations, but further studies are warranted. In addition, the allele A of the rs13306560 polymorphism as well as the in vitro methylation of CpGs reduced the promoter activity of the MTHFR regulatory region.

KEYWORDS:

gene; hypertension; hypertension, essential; methylenetetrahydrofolate reductase (NADPH2); single nucleotide polymorphism

PMID:
26022245
DOI:
10.1161/CIRCGENETICS.114.000942
[Indexed for MEDLINE]

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