Variations in Inflammatory and Cell Cycle Genes and Preterm Birth, Small for Gestational Age and Hypertensive Disorders of Pregnancy

Harmon, Quaker Elizabeth

Variations in Inflammatory and Cell Cycle Genes and Preterm Birth, Small for Gestational Age and Hypertensive Disorders of Pregnancy

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March 22, 2019

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Harmon, Quaker Elizabeth
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology

Abstract

The maternal outcome of preeclampsia and the fetal outcomes of preterm birth and poor intrauterine growth often occur together, share placental pathology and are marked by changes in inflammatory biomarkers. Genetic polymorphisms in inflammatory genes have been investigated with respect to all of these outcomes with conflicting results. In previous studies case groups have been small or non-representative of US populations, and coverage of candidate genes has been sparse. We sought to expand coverage of inflammatory genes related to natural killer cells and T cells and in addition included candidate genes related to cell cycle function. In a sample of 1646 women from a bi-racial prospective pregnancy cohort, we examined the relationship between 503 tagSNPs in 40 genes and the outcomes of preterm birth, small for gestational age, gestational hypertension and preeclampsia. Six genes involved in natural killer cell function (IL12A, CSF2, IFNGR2 and KIR3DL2) and Th2 immunity (IL13 and IL4) were associated with preterm birth among European Americans with some evidence of an association for African Americans as well (IL12A and CSF2). IL6 and KLRD1 were associated with term small for gestational age births among African Americans with similar results for IL6 alone among European Americans. LTA, TNF and TBKBP1 were associated with preeclampsia among European Americans only. There were no associations with any cell cycle genes or with the outcome of gestational hypertension. In summary, this study found novel associations with a number of genes related to natural killer cells, Th2 immunity and TNF signaling pathways and the outcomes of preterm birth, poor fetal growth and preeclampsia among both European and African Americans.

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