Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA.
Am J Obstet Gynecol. 2010 May;202(5):431.e1-34. doi: 10.1016/j.ajog.2010.03.026.
The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery.
A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing.
The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P=.000148) and tissue inhibitor of metalloproteinase 2 (mother; P=.000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P=.004 and .007, respectively).
An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB.
本研究旨在确定候选基因中母胎单核苷酸多态性（SNP）是否与自发性早产/分娩有关。
对 223 名母亲和 179 名胎儿（胎膜完整的早产孕妇，妊娠 37 周以下分娩[早产（PTB）]）和 599 名母亲和 628 名胎儿（正常妊娠）进行了遗传关联研究；研究了 190 个候选基因和 775 个 SNP。进行了单基因座/单倍型关联分析；采用假发现率对多重检验进行校正。
与 PTB 最强的单基因座关联是白细胞介素 6 受体 1（胎儿；P=.000148）和金属蛋白酶组织抑制剂 2（母亲；P=.000197），经多重比较校正后仍有显著意义。全基因组单倍型分析表明，胰岛素样生长因子 F2 的胎儿 DNA 变异与母体外分泌型基质金属蛋白酶 2（MMP2）基因编码的 alpha 3 型 IV 胶原同工型 1（母）之间存在关联（总体，P=.004 和.007）。
控制胎儿炎症的 SNP（白细胞介素 6 受体 1）和母体外分泌型基质金属蛋白酶 2（MMP2）基因编码的参与细胞外基质代谢的 DNA 变异大约使 PTB 的风险增加了一倍。
