Women who deliver twins are more likely to smoke and have high frequencies of specific SNPs: Results from a sample of African-American women who delivered preterm, low birth weight babies

Objectives: We examine if there are genetic and environmental differences between mothers of singleton and multiple pregnancies in a sample of African-American mothers. Methods: We focus on genomic areas suggested to increase or decrease the odds of multiple pregnancies. We computed the odds ratio (OR) and the 95% confidence interval (CI) for each SNP unadjusted or adjusted with smoking. SNPs' allelic differences between mothers of multiple pregnancies and singletons were also tested using Fisher's exact test. We considered additive terms for the SNPs' genotypes, smoking, and a multiplicative interaction term of two selected SNPs' genotypes. Results: We found significant interactions between smoking and SNPs of the CYP19A, MDM4, MTHFR and TP53 genes which correlated with higher odds of twinning. We also found a significant interaction between SNPs at the TP53 (rs8079544) and MTHFR gene (rs4846049), where the interaction between the homozygotes (TT for rs8079544, GG for rs4846049) correlated with lowered odds of multiple pregnancy. Conclusions: We provide a mechanistic explanation and preliminary evidence for previous reports that mothers of twins are more likely to have smoked, despite seemingly conflicting evidence for the fertility-reducing effects of nicotine. Nicotine, as an aromatase inhibitor, inhibits estrogen synthesis and may allow for greater production of gonadotropins. While smoking may have deleterious effects on fertility across many genotypes, in women of specific genotypes it may raise their odds of producing twins. TP53 involvement suggests the necessity of future work examining relationships between women who bear multiples and cancer risk.