Vanderbilt Epidemiology Center, Vanderbilt University, Nashville, Tennessee, 37203, USA.
Institute for Medicine and Public Health, Vanderbilt University, Nashville, Tennessee, 37203, USA.
Sci Rep. 2017 Aug 29;7(1):9874. doi: 10.1038/s41598-017-10150-2.
This study evaluates the relationship between single nucleotide polymorphisms (SNPs) in nonsteroidal anti-inflammatory drug (NSAID) metabolism and related pathways and spontaneous abortion (SAB, gestation < 20 weeks) risk. Women were enrolled in Right from the Start (2004-2010) prospective cohort. Periconceptional NSAIDs reported through the sixth week of pregnancy were obtained from study interviews. We evaluated 201 SNPs in 600 European American women. Interaction analyses between NSAID use and SNPs were conducted using logistic regression, adjusted for confounders. We also evaluated prostaglandin E2 urinary metabolite (PGE-M) in an independent population for association with SNPs using linear regression. NSAID use was reported by 63% of cases and 62% controls. The most significant interaction was at prostacyclin synthase (PGIS) rs5602 (OR = 0.34, 95% CI 0.19-0.60, p = 2.45 × 10) and was significant after a Bonferroni correction. NSAID users were protected from SAB (OR = 0.78, 95% CI 0.56-1.10), while non-NSAID users were at increased risk (OR = 2.11, 95% CI 1.35-3.29) in rs5602 stratified analyses. rs5602 also associated with increased PGE-M levels (Beta = 0.09, 95% CI -0.002-0.19, p = 0.033). We identified an association between a PGIS variant and SAB risk that is modified by NSAIDs use during pregnancy and directly associated with increased levels of PGE metabolites. This suggests the potential use of genetic information to guide pharmaceutical intervention to prevent adverse pregnancy outcomes.
这项研究评估了非甾体抗炎药（NSAID）代谢和相关途径中的单核苷酸多态性（SNP）与自然流产（SAB，妊娠<20 周）风险之间的关系。研究纳入了 2004 年至 2010 年进行的“从一开始就是正确的”前瞻性队列中的女性。通过妊娠第 6 周的研究访谈获得了围孕期 NSAID 的使用情况。我们评估了 600 名欧洲裔美国女性中的 201 个 SNP。使用逻辑回归对 NSAID 使用与 SNP 之间的相互作用进行了分析，并对混杂因素进行了调整。我们还使用线性回归评估了前列腺素 E2 尿代谢产物（PGE-M）在独立人群中与 SNP 的关联。63%的病例和 62%的对照报告了 NSAID 的使用情况。最显著的相互作用发生在前列环素合酶（PGIS）rs5602 处（OR=0.34，95%CI 0.19-0.60，p=2.45×10），且在 Bonferroni 校正后仍有统计学意义。PGIS rs5602 上的 NSAID 使用者能够降低 SAB 风险（OR=0.78，95%CI 0.56-1.10），而非 NSAID 使用者的风险增加（OR=2.11，95%CI 1.35-3.29）。rs5602 还与 PGE-M 水平升高相关（Beta=0.09，95%CI-0.002-0.19，p=0.033）。我们发现了 PGIS 变体与 SAB 风险之间的关联，该关联受妊娠期间 NSAID 使用情况的影响，并与 PGE 代谢物水平升高直接相关。这表明可以利用遗传信息来指导药物干预，以预防不良妊娠结局。
