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Maternal C677T MTHFR Polymorphism and Environmental Factors Are Associated With Cleft Lip and Palate in a Mexican Population
  1. Jose Jesus Ibarra-Lopez, MD*,
  2. Patricia Duarte, PhD,
  3. Veronica Antonio-Vejar, MD*,
  4. Emma S. Calderon-Aranda, PhD,
  5. Gerardo Huerta-Beristain, PhD*,
  6. Eugenia Flores-Alfaro, PhD*,
  7. Ma. Elena Moreno-Godinez, PhD*
  1. From the *Laboratory of Toxicology and Environmental Health, Academic Unit of Chemical-Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Gro, Mexico; †Department of Maxillofacial Surgery, General Hospital Dr. Raymundo Abarca Alarcon, Chilpancingo, Gro, Mexico; and ‡Department of Toxicology, CINVESTAV, Mexico, DF, Mexico.
  1. Received February 24, 2013, and in revised form May 3, 2013.
  2. Accepted for publication May 4, 2013.
  3. Reprints: Ma. Elena Moreno-Godinez, PhD, Laboratory of Toxicology and Environmental Health, Academic Unit of Chemical-Biological Sciences, Autonomous University of Guerrero, Mexico. Av. Lazaro Cardenas s/n, Ciudad Universitaria Chilpancingo, Guerrero, México 39070. E-mail: emoreno20{at}hotmail.com.
  4. Supported by Mexican Council for Science and Technology CONACYT FOMIX-GUE-108813.
  5. The authors declare no conflict of interest of any type.

Abstract

Introduction Nonsyndromic cleft lip and cleft palate (CL/P) is associated with environmental, nutritional, and genetic factors. Maternal polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene have been associated with CL/P.

Objectives To determine the relationship between the risk of having a child with CL/P and maternal C677T and A1298C MTHFR polymorphisms, the intake of folate supplements, and exposure to environmental factors during the first trimester of pregnancy, a case-control study of Mexican mothers (88 case mothers and 116 control mothers) was conducted.

Methods A questionnaire was used to assess exposure to environmental factors. The C677T and A1298C polymorphisms were identified by polymerase chain reaction with restriction fragment length polymorphism.

Results Mothers with the 677CT or 677TT genotype had a higher risk of having a child with CL/P than mothers with the 677CC genotype (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1–5.7). An increased risk of having a child with CL/P was associated with the lack of folate supplementation during the first trimester of pregnancy (OR, 3.8; 95% CI, 1.9–7.6), and this risk was greater in the mothers with the 677TT or 677CT genotype than mothers who reported taking folate supplements and had the 677CC genotype (OR, 11.2; 95% CI, 3.3–37.5). Pesticide exposure was associated with CL/P. There was no significant association between either the A1298C variant or tobacco exposure and the risk of CL/P.

Conclusion These results suggest that gene-environment interactions play an important role in the development of CL/P.

Key Words
  • Cleft lip
  • palate
  • MTHFR
  • folate
  • pesticides
  • A1298C and C677T polymorphisms

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