基因多态性与青海妊娠高血压疾病的相关性

目的 探讨内皮型一氧化氮合酶（eNOS）、肿瘤坏死超家族成员13B（TNFSF13B）、缺氧诱导因子 1α（HIF-1α）、血管内皮生长因子A（VEGFA）、血管内皮生长因子受体1（VEGFR1）的基因多态性与青海孕产妇HDCP易感性的相关性。 方法 采用病例对照研究，120例HDCP孕产妇为研究组，同期100例健康孕产妇为对照组，所有研究对象均来自青海省。使用Sequenom MassARRAY 法检测研究对象HIF-1α基因SNP位点 RS 11549465、RS 115494657和RS 2057482；TNFSF13B基因SNP位点RS 16972194；eNOS基因SNP位点RS 2070744；VEGFA基因SNP位点RS 3025029和RS 2010963；VEGFR1基因SNP位点RS 7335588、RS 722503和RS 12584067基因型分布，比较各SNP位点在两组间的差异。结果 eNOS基因、VEGFA基因和VEGFR1基因各SNP位点在两组之间差异有显著性(P<0.001或P<0.05）。位点RS 2070744和RS 3025039基因型CC在研究组的比例均高于对照组（均P<0.001）；其中，等位基因C在HDCP人群中发病风险度（OR）分别为:2.13（1.45～3.12）和4.95（2.97～8.26）（均P<0.001）。位点RS 2010963和RS 7335588基因型GG在研究组中比例均低于对照组（均P<0.05）；此两个位点等位基因G在HDCP人群中发病风险度（OR）分别为0.50（0.34～0.74）和0.46（0.30～0.72）（均P<0.001）。位点RS 722503基因型TC在研究组的比例为56.67％，高于对照组的29.00％；等位基因C在人群HDCP发病风险度为2.46（1.58～3.84）（P<0.001）。 结论 VEGFA、VEGFR1和eNOS的基因多态性与青海妊娠高血压疾病有一定的关联，是该病在青海发病率高的潜在遗传易感基因。

Correlation between genetic polymorphism and hypertensive disorder complicating pregnancy in Qinghai

Objective To explore the correlation between the polymorphisms in endothelial nitric oxide synthase(eNOS), tumor necrosis super family member 13B(TNFSF13B), hypoxia inducible factor-1α(HIF-1α), vascular endothelial growth factor A(VEGFA) and vascular endothelial growth factor receptor 1(VEGFR1) and susceptibility to hypertensive disorder complicating pregnancy (HDCP) of pregnant women in Qinghai. Methods With the performance of a case-control study, a total of 120 Han patients with HDCP were enrolled as the study group, and 100 healthy pregnant women were included as the control group during the same period. All subjects were from Qinghai province. Sequenom MassARRAY assay was utilized to detect the genotypes of ten clinically relevant polymorphisms of HIF-1 α (RS 11549465, RS 115494657 and RS 2057482), TNFSF13B (RS 16972194), eNOS (RS 2070744), VEGFA (RS 3025029 and RS 2010963) and VEGFR1 (RS 7335588, RS 722503 and RS 12584067). Besides, the differences of single nucleotide polymorphism (SNP) sites were compared between groups subsequently. Results eNOS gene, VEGFA gene,and VEGFR1 gene were found to be significantly different between the study group and the normal group (P<0.001 or P<0.05).The proportions of genotype CC in RS 2070744 and RS 3025039 were higher in the study group than those in the control group (all P<0.001). Among them, the odd ratio (OR) of C allele in the two loci were 2.13 (1.45-3.12) and 4.95 (2.97-8.26) in the HDCP population (all P<0.001), respectively.The proportions of genotype GG in RS 2010963 and RS 7335588 were lower in the study group than those in control group (all P<0.05). Meanwhile, the OR of G alleles in the two loci were 0.50 (0.34-0.74) and 0.46 (0.30-0.72) in the HDCP population (all P<0.001), respectively. Furthermore, the proportion of RS 722503 genotype TC in the study group was 56.67%, higher than that of the control group of 29%, and the OR of C allele was 2.46 (1.58-3.84) in the population HDCP (P<0.001). Conclusion The genetic polymorphisms of VEGFA, VEGFR1 and eNOS are associated with HDCP in Qinghai province, which may be the potential genetic risk factors inducing high incidence of the disease in Qinghai.