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Black race is one of the strongest risk factors for preterm birth (PTB). Recently published data supports the hypothesis that genetic variation is a critical component in the pathogenesis of PTB and may account, in part, for the differences in PTB among different racial groups. We sought to identify single nucleotide polymorphisms (SNPs) associated with PTB within a cohort of black women.
This is a secondary analysis of a randomized trial that evaluated the effect of periodontal disease treatment on PTB. Women were enrolled between 6-20 weeks gestation at three prenatal care clinics between 2004-2007. Maternal DNA samples were collected and analyzed using a custom 1536-SNP chip designed to specifically assess genes involved in inflammation. The association between PTB <37 weeks and PTB <34 weeks with each SNP was assessed among black women enrolled in the study (significance considered p<0.001). Dominant, codominant, additive and recessive inheritance models were considered. History of prior spontaneous PTB was controlled for in adjusted analyses.
Of the 1,061 black women in the study with SNP data, 142 (13.4%) had a PTB <37 weeks gestation and 57 (5.4%) women delivered at <34 weeks gestation. Two SNPs in the PRKCA gene (rs6504424, rs7225452) as well as SNPs in the MMP2 gene (rs11639960) and C6 gene (rs6883180) were associated with an increased risk of PTB <37 weeks. A SNP in the IL17A gene (rs4711998) was found to be significantly associated with both PTB <34 weeks and <37 weeks. Additional SNPs in the PGR gene (rs11571275) and FLT1 gene (rs12428494) were associated with PTB <34 weeks but not <37 weeks. The only SNP protective against PTB was found in the IL3 gene (rs3091336).
We identified 8 novel SNPs in genes critical to inflammation, cell signaling, and angiogenesis that are associated with preterm delivery in black women. These genetic variants may be important in the pathogenesis of preterm birth, however further studies are needed to elucidate their precise role.