Fetal growth restriction (FGR) is one of the main syndromes causing fetal morbidity and mortality. It was known to be associated with different factors including maternal, fetal, and environmental. However, the effect of genetic factors in FGR is not totally understood. Recently, researchers have focused on investigating genetic variants as possible markers of FGR. This especially concerns maternal genetic polymorphisms since they could serve as prenatal prognostic biomarkers. Accordingly, we aimed to study the association of several polymorphisms affecting vital processes of pregnancy with FGR in pregnant women. Targeted polymorphisms include methylenetetrahydrofolate reductase (MTHFR) 677C > T; methionine synthase reductase (MTRR) 66A > G; methionine synthase (MTR) 2756A > G; angiotensinogen (AGT) 704 T > C; and vascular endothelial growth factor A (VEGFA) 634C > G. In addition, this study examined SNP–SNP interactions, linkage disequilibrium (LD), and haplotypes association for these polymorphisms in the studied population. According to our data, MTRR 66(GG) carriers had increased FGR risk (OR = 3.18, 95% CI 1.31–7.72) while (AG) genotype was associated with lower FGR risk (OR = 0.37, 95% CI 0.17–0.84). AGT 704T > C also showed significant association with FGR with allele (T) as a risk factor. SNP–SNP interactions analysis revealed antagonistic relationship between these two polymorphisms and haplotypes association confirmed this finding. High LD possibility was shown between MTHFR 677C > T and MTR 2756A > G (D′ = 0.999) located on chromosome 1. We suggest MTRR 66A > G and AGT 704T > C as associated with FGR susceptibility with antagonistic interaction. Result will help to expand our understanding of FGR as a multifactorial syndrome and improve prenatal prognosis using maternal genetic biomarkers, but further studies in different populations are needed to confirm findings.

中文翻译：

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俄罗斯罗斯托夫地区孕妇母亲遗传多态性与胎儿生长受限综合征的关联

胎儿生长受限（FGR）是导致胎儿发病和死亡的主要综合征之一。众所周知，它与不同的因素有关，包括母亲、胎儿和环境。然而，遗传因素对 FGR 的影响尚不完全清楚。最近，研究人员重点研究遗传变异作为 FGR 的可能标记。这尤其涉及母体遗传多态性，因为它们可以作为产前预后生物标志物。因此，我们的目的是研究影响妊娠重要过程的几种多态性与孕妇 FGR 的关联。靶向多态性包括亚甲基四氢叶酸还原酶（MTHFR）677C > T；蛋氨酸合酶还原酶 (MTRR) 66A > G；甲硫氨酸合酶 (MTR) 2756A > G；血管紧张素原 (AGT) 704 T > C; 和血管内皮生长因子 A (VEGFA) 634C > G。此外，本研究还检查了研究人群中这些多态性的 SNP-SNP 相互作用、连锁不平衡 (LD) 和单倍型关联。根据我们的数据，MTRR 66(GG)携带者的FGR风险增加(OR = 3.18，95% CI 1.31–7.72)，而(AG)基因型与较低的FGR风险相关(OR = 0.37，95% CI 0.17–0.84) 。AGT 704T > C 还显示与 FGR 显着相关，且等位基因 (T) 作为危险因素。SNP-SNP 相互作用分析揭示了这两种多态性之间的拮抗关系，单倍型关联证实了这一发现。位于 1 号染色体上的 MTHFR 677C > T 和 MTR 2756A > G (D′ = 0.999) 之间显示出高 LD 可能性。我们建议 MTRR 66A > G 和 AGT 704T > C 与具有拮抗相互作用的 FGR 易感性相关。结果将有助于扩大我们对 FGR 作为多因素综合征的认识，并利用母体遗传生物标志物改善产前预后，但需要在不同人群中进行进一步研究来证实研究结果。