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Maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of recurrent pregnancy loss

Published online by Cambridge University Press:  18 May 2012

F. Sata ,
H. Yamada ,
R. Kishi  and
H. Minakami
F. Sata*
Affiliation:
Department of Environmental Health, National Institute of Public Health, Wako, Japan
H. Yamada
Affiliation:
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan
R. Kishi
Affiliation:
Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan
H. Minakami
Affiliation:
Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
*
*Address for correspondence: Dr F. Sata, Department of Environmental Health, National Institute of Public Health, 2-3-6 Minami, Wako, Saitama 351-0197, Japan. (Email [email protected])
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Abstract

Epidemiological studies have suggested that the condition of recurrent pregnancy loss (RPL) may be multifactorial, with both genetic predisposition and environmental factors potentially involved in its pathogenesis. The aim of this study is to elucidate the associations between maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of RPL. This case–control study, which involved 116 cases with two or more instances of RPL and 306 fertile controls, was performed in the city of Sapporo, Japan. The associations between eight single nucleotide polymorphisms of folate, alcohol and energy metabolism-related genes [methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), beta-3-adrenergic receptor (ADRB3) and peroxisome proliferator-activated receptor gamma (PPARG)], and RPL were assessed. Without consideration of cigarette smoking or alcohol use, the risk of RPL significantly decreased in women with the MTHFR rs1801133 TT, MTR rs1805087 AG or ALDH2 rs671 AA genotype (P < 0.05). The risk of RPL associated with cigarette smoking and alcohol use decreased significantly in women carrying the MTHFR rs1801133 T allele [odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27–0.95]. Similarly, the risk of RPL significantly decreased in women carrying the MTR rs1805087 G allele (OR, 0.44; 95% CI, 0.23–0.85). Our findings suggest that maternal gene polymorphisms related to folate metabolism may decrease the risk of RPL. Molecular epidemiological studies are needed to unequivocally elucidate the multifactorial effects of both genetic and environmental factors on human fecundity.

Keywords

alcoholenergy metabolismfolaterecurrent pregnancy losssingle nucleotide polymorphism
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 5 , October 2012 , pp. 327 - 332
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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