Greater Chance of Twins Seen for Female Smokers With Genetic Variant

Researchers may have discovered a mechanistic explanation and preliminary evidence to support previous findings that mothers of twins are more likely to have smoked, despite smoking’s potential deleterious effects on fertility. The study has been published online in the American Journal of Human Biology.

Lorena Madrigal, PhD, of the University of South Florida, and colleagues sought to explain within-population variation in pregnancies in a subsample of African-American women; in general, African populations have the highest (40–50 per thousand) frequency of twinning compared to other populations, which is believed to be due to environmental and genetic factors that may predispose women to higher rates of dizygotic twinning. A total of 227 African-American mothers (29 multiple births, 198 singeton) of infants with extremely low birth weight (401–1,000g and <72 h of age from the GENEVA study of Preterm Delivery were genotyped with a focus on specific single nucleotide polymorphisms (SNPs) associated with multiple pregnancies: MTHFR, MDM4, CYP19A1, TP53, LHCGR, TGFBR1, and DDX17).

A significant effect was observed between smoking and several genes in the SNP. Specifically, the interaction of smoking with the TT genotype of the rs8079544 SNP of the TP53 gene had a twinning odds ratio (OR) of 62.23. This could be due to the coding of p53 protein by the TP53 gene, which regulates the cell cycle, and the role of TP53 in implantation of the embryo. Nicotine’s aromatase-inhibiting action could allow for greater production of gonadotropins that may support polyovulation.

The researchers conclude that future studies could build from this study to determine if these polymorphisms are present in so-called “twin-towns” (areas with high populations of twins) due to natural selection or genetic drift.

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