Innate immune system gene polymorphisms in maternal and child genotype and risk of preterm delivery

Objective. There is little information about the combination of genetic variability in pregnant women and their children in relation to the risk of preterm delivery (PTD). In a sub-cohort of 487 non-Hispanic white and 288 African-American mother/child pairs, the Pregnancy Outcomes and Community Health Study assessed 10 functional polymorphisms in 9 genes involved in innate immune function. Methods. Race-stratified weighted logistic regression models were used to calculate odds ratios for genotype and PTD/PTD subtypes. Polymorphisms significantly associated with PTD/PTD subtypes were tested for mother/child genotype interactions. Results. Three maternal polymorphisms (IL-1 receptor antagonist intron two repeat (IL-1RN), matrix metalloproteinase-C1562T, and TNF receptor two M196R (TNFR2)) and three child polymorphisms (IL1-RN, tumor necrosis factor-alpha -G308A, and TNFR2) were associated with PTD, but associations varied by PTD subtype and race. Two interactions were detected for maternal and child genotype. Among non-Hispanic white women, the odds of PTD was higher when both mother and child carried the IL-1RN allele two (additive interaction p < 0.05). Among African-American women, the odds of PTD were higher when both mother and child carried the TNFR2 R allele (multiplicative interaction p < 0.05). Conclusion. These results highlight the importance of assessing both maternal and child genotype in relation to PTD risk.