Associations of MTHFR Gene Polymorphisms with Hypertension and Hypertension in Pregnancy: A Meta-Analysis from 114 Studies with 15411 Cases and 21970 Controls

Abstract

BackgroundSeveral epidemiological studies have investigated the associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with hypertension (H) or hypertension in pregnancy (HIP). However, the results were controversial. We therefore performed a comprehensive meta-analysis to provide empirical evidences on the associations.MethodologiesThe English and Chinese databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Meta-regression, subgroup analysis, sensitivity analysis, cumulative meta-analysis and assessment of publication bias were performed in our study.Principal FindingsA total of 114 studies with 15411 cases and 21970 controls were included, 111 studies with 15094 cases and 21633 controls for the C677T polymorphism and 21 with 2533 cases and 2976 controls for the A1298C polymorphism. Overall, the C677T polymorphism was significantly associated with H and HIP (H & HIP: OR = 1.26, 95% CI = 1.17–1.34; H: OR = 1.36, 95% CI = 1.20–1.53; HIP: OR = 1.21, 95% CI = 1.08–1.32). Stratified analysis by ethnicity revealed a significant association among East Asians and Caucasians, but not among Latinos, Black Africans, and Indians and Sri Lankans. In the stratified analyses according to source of controls, genotyping method, sample size and study quality, significant associations were observed in all the subgroups, with the exception of population based subgroup in H studies and large sample size and “others” genotyping method subgroups in HIP studies. For the A1298C polymorphism, no significant association was observed either in overall or subgroup analysis under all genetic models.ConclusionsThis meta-analysis suggests that the MTHFR C677T rather than A1298C polymorphism may be associated with H & HIP, especially among East Asians and Caucasians.

Riboflavin status, MTHFR genotype and blood pressure: current evidence and implications for personalised nutrition

“…It has been suggested that an accumulation of 10-formyl tetrahydrofolate in endothelial cells may affect folate metabolism and in turn affect endothelial NO synthase activity (105) . Therefore, riboflavin may enhance endothelial NO synthase activity by correcting the imbalance in methylated v. non-methylated tetrahydrofolate in (117) 1520 cases Chinese 1·87 (1·31, 2·68) 1334 controls Yang et al (4) 6584 cases Worldwide 1·36 (1·20, 1·53) 6760 controls Wu et al (118) 5207 cases Worldwide 1·62 (1·32, 1·99) 5383 controls Yang et al (119) those with the TT genotype or by increasing 5-methyltetrahydrofolate and thus decreasing BP irrespective of BP-lowering drugs (105) . Further work is required to investigate mechanisms linking this polymorphism with BP and the potential for riboflavin to provide a targeted option to treat elevated BP in this genotype group.…”

Meta-analysis of the association of AhR Arg554Lys, AhRR Pro185Ala, and ARNT Val189Val polymorphisms and endometriosis risk in Asians

“…The NOS consists of three parts with nine items (one point for each item): selection of the study groups (four items), comparability of the groups (two items), and outcome measurements (three items) [21]. A score greater than 5 was regarded as high quality; otherwise, the study was considered low quality [22].…”

Association between ANKK1 (rs1800497) polymorphism of DRD2 gene and attention deficit hyperactivity disorder: A meta-analysis

“…The above results were conflicting or inconclusive, presumably due to various genetic backgrounds, small sample size and potential confounding bias. Meta-analysis is a widely used statistical method in medical studies, particularly for a topic that are being extensively studied with controversial results [31]. Thus, we performed a meta-analysis to provide a more comprehensive assessment of the association between this polymorphism and ADHD.…”