BACKGROUND To study the role of single nucleotide variants (SNVs) of genes related to preeclampsia in Pakistani pregnant women. METHODS After 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. RESULTS Genotyping 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. CONCLUSION This 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.

中文翻译：

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巴基斯坦患者的MTHFR和F5遗传变异与先兆子痫相关：一项病例对照研究。

背景技术研究与子痫前期有关的基因的单核苷酸变异体（SNV）在巴基斯坦孕妇中的作用。方法经伦理批准并获得知情同意后；登记了250名孕妇，并将其平均分为两组（125名先兆子痫病例和125名血压正常的孕妇）。记录人口统计细节和病史，并获得10 ml血液样本用于DNA提取。开发了四引物扩增难治性突变系统（ARMS）分析方法，用于评估三个先兆子痫相关基因的变体。F5，MTHFR和VEGFA。六个SNV的关联；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）和VEGFA：c。* 237C> 通过使用不同的遗传模型确定先兆子痫的T（rs3025039）。结果SNV的基因分型显示，MTHFR：c.665C> T的患者对先兆子痫的敏感性增加（CT与CC / TT：OR = 2.79，95％CI = 1.18-6.59； P * = 0.046，CT / TT与VS CC：OR = 2.91，95％CI = 1.29-6.57； P * = 0.0497，分别在主导模型和主导模型中），而F5：c.6665A> G，（A / G与AA / GG：OR = 0.42， 95％CI = 0.21-0.84;在主导模型中P * = 0.038）和MTHFR：c.1286A> C，（CC与AA：OR = 0.36，95％CI = 0.18-0.72;在主导模型中P * = 0.0392）有明显降低先兆子痫的风险。F5：c.1601G> A，VEGFA：c.-2055A> C和VEGFA：c。* 237C> T变异体与疾病无关。结论这是第一个病例对照研究，描述了F5：c的保护作用。6665A> G在世界任何人群中均能抗先兆子痫。此外，本研究证实了MTHFR基因变异在巴基斯坦患者先兆子痫发展中的关联和作用。可能需要进一步的遗传研究，以更好地了解孕妇子痫前期相关基因中SNV的复杂遗传机制。