Hong Huang1, Kathryn B H Clancy2, Crystal Burhance3, Yilliang Zhu4, Lorena Madrigal3. 1. School of Information, University of South Florida, 4202 E. Fowler Av, Tampa, Florida, 33620. 2. Department of Anthropology, University of Illinois at Urbana-Champaign, 109 Davenport Hall, 607 S. Mathews Ave., Urbana, Illinois, 61801. 3. Department of Anthropology, University of South Florida, 4202 E. Fowler Av, Tampa, Florida, 33620. 4. Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida.
Abstract
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.
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.
Authors: Jerome F Strauss; Roberto Romero; Nardhy Gomez-Lopez; Hannah Haymond-Thornburg; Bhavi P Modi; Maria E Teves; Laurel N Pearson; Timothy P York; Harvey A Schenkein Journal: Am J Obstet Gynecol Date: 2017-12-14 Impact factor: 8.661
Authors: Mariana de Oliveira-Klein; Augusto César Cardoso-Dos-Santos; Alice Tagliani-Ribeiro; Nelson Rosa Fagundes; Ursula Matte; Lavinia Schuler-Faccini Journal: Genet Mol Biol Date: 2018-11-29 Impact factor: 1.771