A Single-Nucleotide Polymorphism in the Fetal Catechol-O-methyltransferase Gene is Associated With Spontaneous Preterm Birth in African Americans


Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau). COMT converts 2- and 4-hydroxy (OH) estrogens to 2- and 4-methoxyestrogens, respectively, and can increase estrogenic milieu locally in tissues. To assess whether the increased incidence of preterm birth (PTB) among AA women is associated with single-nucleotide polymorphism (SNP) in the COMT gene, we examined variations in maternal and fetal COMT genes and their association with pregnancy outcomes (term vs preterm pregnancies) using 4 functional SNPs: rs4633, rs4680, rs4818, and rs6269 in both AA and Cau. We analyzed samples from 267 AA women (191 term and 76 preterm pregnancies) and 339 Cau (194 term and 145 preterm pregnancies) in this study. The results showed a significant difference (P < .05) in allele and genotype frequencies between term and preterm AA and Cau women in 3 SNPs in both maternal and fetal DNA. The analysis revealed that in AA fetal COMT genes, SNP rs4818 is associated with PTB at the allele (C; P < .001), genotype (C/C; P < .01), and 2- (P < .03) and 3 (P < .04)-window haplotype levels. Multidimensionality reduction analysis also showed a significant (P < .01) association between rs4818 and PTB. In conclusion, our study demonstrated that a synonymous polymorphism, rs4818 in the fetal COMT gene, is associated with PTB in AA.

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Change history

  • 30 December 2012

    The statement of funding on page 141 of the February 2012 issue of Reproductive Sciences is incomplete. In addition to the funding sources mentioned, the authors would also like to disclose receipt of financial support from “National Center for Research Resources, Grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.”


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Correspondence to Ayman Al-Hendy MD, PhD.

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Thota, C., Menon, R., Wentz, M.J. et al. A Single-Nucleotide Polymorphism in the Fetal Catechol-O-methyltransferase Gene is Associated With Spontaneous Preterm Birth in African Americans. Reprod. Sci. 19, 135–142 (2012).

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  • preterm birth
  • African Americans
  • Caucasians
  • single-nucleotide polymorphism
  • catechol-O-methyltransferase