Gene Mutations and Pregnancy Induced Hypertension: A Meta-Analysis

The purpose of this study is to disseminate current evidence on population genome health and related epigenetic factors, through the meta-analyses of methylenetetrahydrofolate reductase (MTHFR) gene in pregnant women who developed hypertension (PIH).

PIH including preeclampsia are the leading causes of maternal and perinatal mortalities.  Preeclampsia presents not only more severe form of PIH, but also additional dysfunctions including edema, proteinuria, headache, and impaired vision. Literatures were searched from various databases using a set of key words for the meta-analyses. Quality scores for the studies and inter-rater evaluation on data coding were completed to ensure data accuracy for pooled meta-analyses.

Preliminary results included 6079 cases and 11061controls from 53 studies. MTHFR 677 homozygous (TT) mutation genotype was significantly associated with increased risk of developing PIH (RR= 1.23, p < 0.01). Subgroup analyses revealed that MTHFR 677TT subtype was a significant risk of PIH in European (RR= 1.20, p < 0.01; 2478 cases and 6175 controls in 19 studies) and in Asian (RR= 1.56, p < 0.01, 1261 cases and 2238 controls in 13 studies). For lifestyle factors, body mass index (BMI) before pregnancy (Kg/M²) was an important predictor for the development of PIH. Normal weight (BMI < 25) was protective against the development of PIH and preeclampsia (RR = 0.75, p < 0.0001); whereas, overweight (BMI = 25-29, RR = 1.52, p < 0.0001) and obesity (BMI > 30, RR = 1.80, p< 0.0001) were associated with increased risk of developing PIH and preeclampsia (376 cases and 2294 controls in 2 studies of Caucasian women).

Future studies are needed to examine epigenetic factors associated with MTHFR gene mutations in the prevention PIH.

Keywords: meta-analyses, epigenetics, pregnancy induced hypertension