A functional SNP in the promoter of the SERPINH1 gene increases risk of preterm premature rupture of membranes in African Americans
A functional SNP in the promoter of the SERPINH1 gene increases risk of preterm premature rupture of membranes in African Americans
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DOI：
10.1073/pnas.0603676103
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发表时间：
2006-09-05
影响因子：
11.1
通讯作者：
Strauss, Jerome F., II
中科院分区：
文献类型：
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作者：
Wang, Hongyan;Parry, Samuel;Strauss, Jerome F., II
早产在非洲裔美国人中比在欧洲裔美国人中更普遍。我们研究了SERPINH 1基因启动子中的功能性SNP对早产胎膜早破（PPROM）的贡献，PPROM是早产的主要可识别原因。SERPINH 1编码热休克蛋白47，一种胶原蛋白合成所必需的伴侣蛋白。SERPINH 1 - 656次要T等位基因在非洲人群和非洲裔美国人中的频率高于欧洲裔美国人（12.4%对4.1%）。在羊膜成纤维细胞中，与主要的-656 C等位基因相比，-656 T等位基因显示出显著降低的启动子活性，羊膜成纤维细胞形成纤维状胶原蛋白，该纤维状胶原蛋白赋予羊膜拉伸强度。最初的病例对照研究表明，与对照组相比，非裔美国人妊娠合并PPROM所生的新生儿中-656 T等位基因的频率显著更高（P < 0.0009）（比值比为3.22，95%置信区间为1.50，7.22）。使用基于29个祖先信息标记的双杂交模型，病例和对照之间的祖先没有显著差异。调整病例对照研究的混合物的结果仍然产生了统计学显着的相关性-656 T等位基因和PPROM（P < 0.002）。一项后续病例对照研究得出了类似的结果。结合病例对照研究结果显示，-656 T等位基因与PPROM之间存在高度显著（P < 0.0000045）关联。SERPINH 1 - 656 T等位基因是与非裔美国人早产相关的祖先信息标记的第一个例子。
Prematurity is more prevalent in African Americans than in European Americans. We investigated the contribution of a functional SNP in the promoter of the SERPINH1 gene, enriched among those of African ancestry, to preterm premature rupture of membranes (PPROM), the leading identifiable cause of preterm birth. SERPINH1 encodes heat-shock protein 47, a chaperone essential for collagen synthesis. The SERPINH1 -656 minor T allele had a greater frequency in African populations and African Americans than in European Americans (12.4% vs. 4.1%). The -656 T allele displayed significantly reduced promoter activity compared to the major -656 C allele in amnion fibroblasts, which lay down the fibrillar collagen that gives tensile strength to the amnion. An initial case-control study demonstrated that the -656 T allele is significantly more frequent in African-American neonates (P < 0.0009) born from pregnancies complicated by PPROM compared with controls (odds ratio of 3.22, 95% confidence interval 1.50, 7.22). There was no significant difference in ancestry among cases and controls using a dihybrid model based on 29 ancestry-informative markers. Adjusting the results of the case-control study for admixture still yielded a statistically significant association between the -656 T allele and PPROM (P < 0.002). A follow-up case-control study gave similar results. The combined case-control findings showed a highly significant (P < 0.0000045) association between the -656 T allele and PPROM. The SERPINH1 -656 T allele is the first example of an ancestry-informative marker associated with preterm birth in African Americans.