The joint association between F5 gene polymorphisms and maternal smoking during pregnancy on preterm delivery
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Factor V (F5) genetic variants and maternal smoking during pregnancy individually has been associated with increased risk of preterm delivery (PTD). We hypothesize that F5 gene and maternal smoking may synergistically increase the risk of PTD. Three single nucleotide polymorphisms (SNPs) in F5 gene (rs6019, rs2213869 and rs6022) were genotyped in 542 mothers with PTD and 1,141 mothers with term deliveries at the Boston Medical Center. The individual and interactive effects of F5 SNPs and maternal smoking on PTD and gestational age were examined, respectively. The results suggested that maternal smoking, three F5 SNPs and F5 haplotype were individually associated with PTD and gestational age. More importantly, we found significant interactions between the two F5 SNPs (rs6019 and rs6022) and maternal smoking on PTD and gestational age. Compared with non-smoking mothers carrying rs6019 GG genotype, persistently smoking mothers carrying genotypes GC or CC were associated with significantly increased risk of PTD (OR(95% CI): 2.1(1.2–3.6) for GC; 5.7(2.1–15.0) for CC; p-interaction = 0.02). A significant interaction was also observed for gestational age. Similar pattern of interactions was found between rs6022 and maternal smoking on PTD. In summary, our data indicated that F5 gene variants and maternal smoking may synergistically increase the risk of PTD.
KeywordsCotinine Maternal Smoking African American Mother Medical Record Documentation Smoking Interaction
The study was supported in part by grants from the National Institute of Child Health and Human Development (R01 HD41702), National Institute of Environmental Health Sciences (R01ES11682, R21ES11666), and March of Dimes Birth Defects Foundation (20-FY98-0701, 20-FY02-56 and #21-FY07-605). We thank the nursing staff of Labor and Delivery at Boston Medical Center for their continuous support and assistance to the study and Lingling Fu for data management, and Ann Ramsey for administrative support. We would like to particularly thank the outstanding expert consultants of the BMC Preterm Study team: Drs. Paul Wise, Jerome Klein, John M. Kasznica, and Milton Kotelchuck.
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