Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
J Hum Hypertens. 2012 Sep;26(9):547-52. doi: 10.1038/jhh.2011.65. Epub 2011 Jun 30.
Increased expression and activity of inducible nitric oxide synthase (iNOS) may contribute to the pathogenesis of pre-eclampsia (PE) and gestational hypertension (GH). However, no previous study has examined whether genetic polymorphisms in the iNOS gene are associated with PE or GH. We examined whether two functional, clinically relevant iNOS genetic polymorphisms (the C(-1026)A polymorphism, rs2779249, in the promoter region, and the G2087A polymorphism, rs2297518, in exon 16) are associated with GH or with PE. We studied 565 pregnant women: 212 healthy pregnant (HP), 166 pregnant with GH and 187 pregnant with PE. Genotypes were determined by real-time PCR, using the Taqman allele discrimination assay. The PHASE 2.1 program was used to estimate haplotype distributions in the three study groups. We found no significant association between the C(-1026)A polymorphism and PE or GH (P>0.05). However, we found the GA genotype and the A allele for the G2087A polymorphism at higher frequency in PE, but not in GH, compared with HP (P<0.05). The haplotype analysis showed no significant intergroup differences (P>0.05). These findings suggest that iNOS genetic variants may affect the susceptibility to PE, but not to GH.
诱导型一氧化氮合酶（iNOS）表达和活性的增加可能与子痫前期（PE）和妊娠期高血压（GH）的发病机制有关。然而，以前没有研究检查过 iNOS 基因的遗传多态性是否与 PE 或 GH 有关。我们检查了两个功能上的、临床相关的 iNOS 基因多态性（启动子区域的 C(-1026)A 多态性，rs2779249，和外显子 16 中的 G2087A 多态性，rs2297518）是否与 GH 或 PE 有关。我们研究了 565 名孕妇：212 名健康孕妇（HP）、166 名患有 GH 的孕妇和 187 名患有 PE 的孕妇。使用 Taqman 等位基因鉴别检测，通过实时 PCR 确定基因型。PHASE 2.1 程序用于估计三组研究中的单倍型分布。我们没有发现 C(-1026)A 多态性与 PE 或 GH 之间存在显著关联（P>0.05）。然而，与 HP 相比，我们发现 PE 中的 GA 基因型和 G2087A 多态性的 A 等位基因频率更高，但 GH 中没有（P<0.05）。单倍型分析显示组间无显著差异（P>0.05）。这些发现表明，iNOS 遗传变异可能影响 PE 的易感性，但不影响 GH。
