IL-1ß haplotype influences the effect of NOx exposure on gestational age in the South African MACE birth cohort.

ABSTRACT

OBJECTIVE: Cytokines, molecules within the immune system that affect either a pro- or anti-inflammatory response, have previously been shown to influence birth outcomes. The maternal cytokine gene-environment interactions are thought to alter their expression, potentially influencing susceptibility to adverse birth outcomes. The aim of this study was to determine the association between the maternal interleukin-1ß (IL-1ß) haplotype and expression variation with oxides of nitrogen (NOx) levels, and thereafter investigate the IL-1ß haplotype-specific effects of NOx exposure levels, IL-1ß mRNA expression and other variables on gestational age. MATERIAL AND METHODS: Using the prospective Mother and Child in the Environment (MACE) birth cohort in Durban, South Africa, 335 participants were genotyped for the IL-1ß haplotype. Previous studies showed that three single nucleotide polymorphisms (SNPs), IL-1ß-1464G/C, -511C/T and -31C/T, constitute the IL-1ß functional haplotype. These SNPs were genotyped using a restriction fragment length polymorphism assay, while IL-1ß mRNA expression was measured using a quantitative real-time polymerase chain reaction assay. Individual estimates of NOx exposure were obtained by land use regression modelling. A multivariate linear regression analysis was employed to test for significant effects on gestational age. RESULTS: IL-1ß mRNA expression was found to possess a haplotype-dependent effect ( p = 0.0001) and its expression levels positively correlated with NOx levels ( r = 0.34; p = 0.006). In the high haplotype model, a unit increase in NOx exposure level was associated with a decrease in gestational age by 1 week ( p = 0.02). Furthermore, gestational age decreased by 0.9 weeks for every unit increase of IL-1ß mRNA expression level ( p = 0.025). HIV-1 positivity was associated with a 0.2-week decrease in gestational age ( p = 0.035) in the intermediate haplotype model and a 0.4-week decrease in the high haplotype model ( p = 0.044). CONCLUSION: These data have implications for better understanding the effect of prenatal NOx exposure on gestational age and demonstrate the role of the IL-1ß haplotype in modulating the effects of NOx exposure.