Abstract
BackgroundTo study the role of single nucleotide variants (SNVs) of genes related to preeclampsia in Pakistani pregnant women.MethodsAfter ethical approval and getting informed consent; 250 pregnant women were enrolled and equally divided into two groups (125 preeclamptic cases and 125 normotensive pregnant women). Demographic details and medical history were recorded, and 10 ml blood sample was obtained for DNA extraction. The tetra-primer amplification refractory mutation system (ARMS) assays were developed for assessing the variants of three preeclampsia related genes; F5, MTHFR and VEGFA. An association of six SNVs; F5:c.1601G > A (rs6025), F5:c.6665A > G (rs6027), MTHFR: c.665C > T (rs1801133), MTHFR: c.1286A > C (rs1801131), VEGFA: c.-2055A > C (rs699947) and VEGFA: c.*237C > T (rs3025039) with preeclampsia was determined by using different genetic models.ResultsGenotyping of the SNVs revealed that patients with MTHFR:c.665C > T, have increased susceptibility to preeclampsia (CT versus CC/TT: OR = 2.79, 95% CI = 1.18–6.59; P* = 0.046 and CT/TT vs CC: OR = 2.91, 95% CI = 1.29–6.57; P* = 0.0497, in overdominant and dominant models, respectively), whereas F5:c.6665A > G, (A/G vs AA/GG: OR = 0.42, 95% CI = 0.21–0.84; P* = 0.038 in overdominant model) and MTHFR:c.1286A > C, (CC versus AA: OR = 0.36, 95% CI = 0.18–0.72; P* = 0.0392 in codominant model) have significantly decreased risk for preeclampsia. F5:c.1601G > A, VEGFA: c.-2055A > C and VEGFA: c.*237C > T variants revealed no relationship with the disease.ConclusionThis is the first case control study describing the protective role of F5:c.6665A > G against preeclampsia in any world population. In addition, the present study confirmed the association and role of MTHFR gene variations in the development of preeclampsia in Pakistani patients. Further genetic studies may be required to better understand the complex genetic mechanism of SNVs in preeclampsia related genes in pregnant women.
Highlights
To study the role of single nucleotide variants (SNVs) of genes related to preeclampsia in Pakistani pregnant women
Factor 5 (F5) (OMIM# 612309), Methylenetetrahydrofolate reductase (MTHFR) (OMIM# 607093) and Vascular endothelial growth factor A (VEGFA) (OMIM# 192240) genes have been widely studied in association with preeclampsia
We found the significant association of MTHFR: c.1286A > C with preeclampsia. This is contradictory with the results reported in Australian [39], Dutch [40] and Mexican [41] women; where the studies have reported lack of association of MTHFR gene variants with preeclampsia which may be due to genetic heterogeneity and different ethnic backgrounds of the patients
Summary
To study the role of single nucleotide variants (SNVs) of genes related to preeclampsia in Pakistani pregnant women. Preeclampsia has been estimated to affect 2–8% of pregnancies, causing 10–15% of maternal deaths worldwide [1, 2] It is a multifactorial and complex disorder and various studies have proposed genetic, environmental, immunological and nutritional factors for its occurrence, though the exact cause largely remains debatable [3,4,5]. F5 (OMIM# 612309), MTHFR (OMIM# 607093) and VEGFA (OMIM# 192240) genes have been widely studied in association with preeclampsia. The products of these genes play a crucial role in the mechanism required for the normal development and functioning of the placenta [7, 8]. The functional genetic variations in the genes affect the thrombogenic and angiogenic
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