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

Abstract

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.

Keywords:

• Premature birth
• inflammation
• maternal & child genotype
• gene–gene interactions
• genetic polymorphisms
• premature birth genetics

Acknowledgements

The authors wish to thank Dr. Bertha Bullen for her care, time, and commitment in collecting data and managing the POUCH Study and Ann Marie Bongiovanni for supervising the gene polymorphism data collection.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This project was funded by a cooperative agreement with the Centers for Disease Controls (#U01 DP00143-01) and grants from the National Institute of Child Health and Human Development (grants R01 HD 34543-01 and R01 HD034543-07) and the National Institute of Nursing Research (renewal NIH POUCH grant number R01 HD34543). N.M. Jones was supported by an Institutional T32 grant (T32 HD046377) in Perinatal Epidemiology awarded to Michigan State University.