TY - JOUR
T1 - Functional Polymorphism rs13306560 of the MTHFR Gene Is Associated with Essential Hypertension in a Mexican-Mestizo Population
AU - Pérez-Razo, Juan Carlos
AU - Cano-Martínez, Luis Javier
AU - Vargas Alarcón, Gilberto
AU - Canizales-Quinteros, Samuel
AU - Martínez-Rodríguez, Nancy
AU - Canto, Patricia
AU - Roque-Ramírez, Bladimir
AU - Palma-Flores, Carlos
AU - Esteban-Martínez, Rosa
AU - López-Hernández, Luz Berenice
AU - Rojano-Mejía, David
AU - Coral-Vázquez, Ramón M.
N1 - Publisher Copyright:
© 2015 American Heart Association, Inc.
PY - 2015/8/25
Y1 - 2015/8/25
N2 - 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.
AB - 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.
KW - gene
KW - hypertension
KW - hypertension, essential
KW - methylenetetrahydrofolate reductase (NADPH2)
KW - single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=84940045413&partnerID=8YFLogxK
U2 - 10.1161/CIRCGENETICS.114.000942
DO - 10.1161/CIRCGENETICS.114.000942
M3 - Artículo
C2 - 26022245
SN - 1942-325X
VL - 8
SP - 603
EP - 609
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
IS - 4
ER -