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

Abstract

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.”

References

  1. 1.

    Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2005. Natl Vital Stat Rep. 2006;55(11):1–18.

  2. 2.

    Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Kirmeyer S. Births: final data for 2004. Natl Vital Stat Rep. 2006;55(1):1–101.

  3. 3.

    Creasy RK. Preterm birth prevention: where are we? Am. J Obstet Gynecol. 1993;168(4):1223–1230.

  4. 4.

    Goldenberg RL, Cliver SP, Mulvihill FX, et al. Medical, psychosocial, and behavioral risk factors do not explain the increased risk for low birth weight among black women. Am J Obstet Gynecol. 1996;175(5): 1317–1324.

  5. 5.

    Al-Hendy A, Salama SA. Catechol-O-methyltransferase polymorphism is associated with increased uterine leiomyoma risk in different ethnic groups. J Soc Gynecol Investig. 2006;13(2): 136–144.

  6. 6.

    Ding Y-S, Gatley SJ, Fowler JS, Chen R, Volkow ND. Mapping catechol-O-methyltransferase in vivo: initial studies with [18F] Ro41-0960. Life Sci. 1996;58(3):195–208.

  7. 7.

    Wentz MJ, Shi SQ, Shi L, et al. Treatment with an inhibitor of catechol-O-methyltransferase activity reduces preterm birth and impedes cervical resistance to stretch in pregnant rats. Reproduction. 2007;134(6):831–839.

  8. 8.

    Harirah H, Thota C, Wentz MJ, Zaman W, Al-Hendy A. Elevated expression of catechol-O-methyltransferase is associated with labor and increased prostaglandin E(2) production by human fetal membranes. Am J Obstet Gynecol. 2009;201(5):496.e1–496.e7

  9. 9.

    Salminen M, Lundström K, Tilgmann C, Savolainen R, Kalkkinen N, Ulmanen I. Molecular cloning and characterization of rat liver catechol-O-methyltransferase. Gene. 1990;93(2):241–247.

  10. 10.

    Tenhunen J, Ulmanen I. Production of rat soluble and membrane-bound catechol-O-methyltransferase forms from bifunctional mRNAs. Biochem J. 1993;296(pt 3):595–600.

  11. 11.

    Tenhunen J, Salminen M, Jalanko A, Ukkonen S, Ulmanen I. Structure of the rat catechol-O-methyltransferase gene: separate promoters are used to produce messenger RNAs for soluble and membrane-bound forms of the enzyme. DNA Cell Biol. 1993; 12(3):253–263.

  12. 12.

    Tenhunen J, Salminen M, Lundström K, Kiviluoto T, Savolainen R, Ulmanen I. Genomic organization of the human catechol O-methyltransferase gene and its expression from two distinct promoters. Eur J Biochem. 1994; 223(3):1049–1059.

  13. 13.

    Guldberg HC, Marsden CA. Catechol-O-methyltransferase: pharmacological aspects and physiological role. Pharmacol Rev. 1975;27(2):135–206.

  14. 14.

    MacLusky NJ, Riskalla M, Krey L, Parvizi N, Niftolin F. Anovulation in female rats induced by neonatal administration of the catechol estrogens, 2-hydroxy-estradiol and 4-hydroxyestradiol. Neuroendocrinology. 1983;37(5):321–327.

  15. 15.

    Van Aswegen CH, Purdy RH, Wittliff JL. Binding of 2-hydroxyestradiol and 4-hydroxyestridiol to estrogen receptor human breast cancers. J Steroid Biochem. 1989;32(4):485–492.

  16. 16.

    Feigelson HS, Henderson BE. Estrogens and breast cancer. Carcinogenesis. 1996;17(11):2279–2284.

  17. 17.

    Kraychy S, Gallagher TF. 2-Methoxyestrone, a new metabolite of estradiol-17 β in man. J Biol Chem. 1957;229(1):519–526.

  18. 18.

    Dunn JF. Transport of estrogens in human plasma. In: Merriem GR, Lipsett MB, eds. Catechol Estrogens. New York, NY: Raven Press; 1983:167–176.

  19. 19.

    Klauber N, Parangi S, Flynn E, Hamel E, D’Amato RJ. Inhibition of angiogenesis and breast cancer in mice by microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Res. 1997;57:81–86.

  20. 20.

    Kanasaki K, Palmsten K, Sugimoto H, et al. Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia. Nature. 2008;453(7198):1117–1121.

  21. 21.

    Thapar A, Langley K, Fowler T, et al. Catechol-O-methyltransferase gene variant and birth weight predict early onset antisocial behavior in children with attention deficit/hyperactivity disorder. Arch Gen Psychiatry. 2005;62(11):1275–1278.

  22. 22.

    Menon R, Velez DR, Thorsen P, et al. Ethnic differences in key candidate genes for spontaneous preterm birth: TNF-alpha and its receptors. Hum Hered. 2006;62(2):107–118.

  23. 23.

    Zaykin DV, Westfall PH, Young SS, et al. Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals. Hum Hered. 2002;53(2):79–91.

  24. 24.

    Raymond M, Rousset F. An exact test for population differentiation. Evolution. 1995;49(6):1280–1283.

  25. 25.

    Ritchie MD, Hahn LW, Moore JH. Power of multifactor dimensionality reduction for detecting gene-gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity. Genet Epidemiol. 2003;24(2):150–157.

  26. 26.

    Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome. Science. 2002;296(5576):2225–2229.

  27. 27.

    Weiss GM, Provost F. Learning when training data are costly: the effect of class distribution on tree induction. J Artif Intell Res. 2003;19(1):315–354.

  28. 28.

    Japkowicz N, Stephen S. The class imbalance problem: a systematic study. Intell Data Anal. 2002;6(5):429–449.

  29. 29.

    Fleiss JL. Statistical Methods for Rates and Proportions. New York: Wiley; 1981.

  30. 30.

    Diatchenko L, Slade GD, Nackley AG, et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005;14(1):135–143.

  31. 31.

    Liu K, Muse SV. PowerMarker: an integrated analysis environment for genetic marker analysis. Bioinformatics. 2005;21(9): 2128–2129.

  32. 32.

    Nackley AG, Shabalina SA, Tchivileva IE, et al. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006;314(5807): 1930–1933.

  33. 33.

    Keelan JA, Coleman M. The molecular mechanisms of term and preterm labor: recent progress and clinical implications. Clin Obstet Gynecol. 1997;40(3):460–478.

  34. 34.

    Roussos P, Giakoumaki SG, Pavlakis S, Bitsios P. Planning, decision making and the COMT rs4818 polymorphism in healthy males. Neuropsychologia. 2008;46(2):757–763.

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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). https://doi.org/10.1177/1933719111417885

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Keywords

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