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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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References

1. Cramer, DW, Wise, LA. The epidemiology of recurrent pregnancy loss. Semin Reprod Med. 2000; 18, 331–339.CrossRefGoogle ScholarPubMed
2. Yamada, H, Kato, EH, Kobashi, G, et al. . Recurrent pregnancy loss: etiology of thrombophilia. Semin Thromb Hemost. 2001; 27, 121–129.CrossRefGoogle ScholarPubMed
3. Christiansen, OB, Nielsen, HS, Kolte, A, Pedersen, AT. Research methodology and epidemiology of relevance in recurrent pregnancy loss. Semin Reprod Med. 2006; 24, 5–16.CrossRefGoogle ScholarPubMed
4. Rai, R, Regan, L. Recurrent miscarriage. Lancet. 2006; 368, 601–611.CrossRefGoogle ScholarPubMed
5. Yamada, H, Sata, F, Saijo, Y, Kishi, R, Minakami, H. Genetic factors of fetal growth restriction and miscarriage. Semin Thromb Hemost. 2005; 31, 334–345.CrossRefGoogle ScholarPubMed
6. Kamen, B. Folate and antifolate pharmacology. Semin Oncol. 1997; 24(Suppl. 18), S30–S39.Google ScholarPubMed
7. O'Neill, C. Endogenous folic acid is essential for normal development of preimplantation embryos. Hum Reprod. 1998; 13, 1312–1316.CrossRefGoogle ScholarPubMed
8. Vollset, SE, Refsum, H, Irgens, LM, et al. . Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr. 2000; 71, 962–968.CrossRefGoogle ScholarPubMed
9. Wouters, MG, Boers, GH, Blom, HJ, et al. . Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril. 1993; 60, 820–825.CrossRefGoogle ScholarPubMed
10. Quere, I, Bellet, H, Hoffet, M, et al. . A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Fertil Steril. 1998; 69, 152–154.CrossRefGoogle ScholarPubMed
11. Nelen, L, Blom, HJ, Steegers, EA, et al. . Homocysteine and folate levels as risk factors for recurrent early pregnancy loss. Obstet Gynecol. 2000; 95, 519–524.Google ScholarPubMed
12. Kumar, KS, Govindaiah, V, Naushad, SE, Devi, RR, Jyothy, A. Plasma homocysteine levels correlated to interactions between folate status and methylene tetrahydrofolate reductase gene mutation in women with unexplained recurrent pregnancy loss. J Obstet Gynaecol. 2003; 23, 55–58.CrossRefGoogle ScholarPubMed
13. Frosst, P, Blom, HJ, Milos, R, et al. . A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10, 111–113.CrossRefGoogle ScholarPubMed
14. Harmon, DL, Woodside, JV, Yarnell, JW, et al. . The common “thermolabile” variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. Q J Med. 1996; 89, 571–577.CrossRefGoogle Scholar
15. Nelen, WL, Blom, HJ, Steegers, EA, den Heijer, M, Eskes, TK. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril. 2000; 74, 1196–1199.CrossRefGoogle ScholarPubMed
16. Rey, E, Kahn, SR, David, M, et al. . Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003; 361, 901–908.CrossRefGoogle ScholarPubMed
17. Ren, A, Wang, J. Methylenetetrahydrofolate reductase C677T polymorphism and the risk of unexplained recurrent pregnancy loss: a meta-analysis. Fertil Steril. 2006; 86, 1716–1722.CrossRefGoogle ScholarPubMed
18. Jones, KL, Smith, DW. Recognition of the fetal alcohol syndrome in early infancy. Lancet. 1973; 302, 999–1001.CrossRefGoogle ScholarPubMed
19. Streissguth, AP, O'Malley, K. Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders. Semin Clin Neuropsychiatry. 2000; 5, 177–190.CrossRefGoogle ScholarPubMed
20. Harlap, S, Shiono, PH. Alcohol, smoking, and incidence of spontaneous abortions in the first and second trimester. Lancet. 1980; 2, 173–176.CrossRefGoogle ScholarPubMed
21. Kline, J, Shrout, P, Stein, Z, et al. . Drinking during pregnancy and spontaneous abortion. Lancet. 1980; 2, 176–180.CrossRefGoogle ScholarPubMed
22. Kesmodel, U, Wisborg, K, Olsen, SF, et al. . Moderate alcohol intake in pregnancy and the risk of spontaneous abortion. Alcohol Alcohol. 2002; 37, 87–92.CrossRefGoogle ScholarPubMed
23. Lashen, H, Fear, K, Sturdee, DW. Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case–control study. Hum Reprod. 2004; 19, 1644–1646.CrossRefGoogle ScholarPubMed
24. Metwally, M, Saravelos, SH, Ledger, WL, Li, TC. Body mass index and risk of miscarriage in women with recurrent miscarriage. Fertil Steril. 2010; 94, 290–295.CrossRefGoogle ScholarPubMed
25. Boots, C, Stephenson, MD. Does obesity increase the risk of miscarriage in spontaneous conception: a systematic review. Semin Reprod Med. 2011; 29, 507–513.CrossRefGoogle ScholarPubMed
26. Miyaki, K, Sutani, S, Kikuchi, H, et al. . Increased risk of obesity resulting from the interaction between high energy intake and the Trp64Arg polymorphism of the beta3-adrenergic receptor gene in healthy Japanese men. J Epidemiol. 2005; 15, 203–210.CrossRefGoogle ScholarPubMed
27. de Luis, DA, Aller, R, Izaola, O, Gonzalez Sagrado, M, Conde, R. Relation of Trp64Arg polymorphism of beta 3-adrenergic receptor gene to adipocytokines and fat distribution in obese patients. Ann Nutr Metab. 2008; 52, 267–271.CrossRefGoogle ScholarPubMed
28. Yamakita, M, Ando, D, Tang, S, Yamagata, Z. The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with weight changes in obese Japanese men: a 4-year follow-up study. J Physiol Anthropol. 2010; 29, 133–139.CrossRefGoogle Scholar
29. Celi, FS, Shuldiner, AR. The role of peroxisome proliferator-activated receptor gamma in diabetes and obesity. Curr Diab Rep. 2002; 2, 179–185.CrossRefGoogle ScholarPubMed
30. Cecil, JE, Watt, P, Palmer, CN, Hetherington, M. Energy balance and food intake: the role of PPARgamma gene polymorphisms. Physiol Behav. 2006; 88, 227–233.CrossRefGoogle ScholarPubMed
31. Jaquet, D, Trégouët, DA, Godefroy, T, et al. . Combined effects of genetic and environmental factors on insulin resistance associated with reduced fetal growth. Diabetes. 2002; 51, 3473–3478.CrossRefGoogle ScholarPubMed
32. Toth, B, Bastug, M, Mylonas, I, et al. . Peroxisome proliferator-activated receptor-gamma in normal human pregnancy and miscarriage. Acta Histochem. 2009; 111, 372–378.CrossRefGoogle ScholarPubMed
33. Toth, B, Jeschke, U, Rogenhofer, N, et al. . Recurrent miscarriage: current concepts in diagnosis and treatment. J Reprod Immunol. 2010; 85, 25–32.CrossRefGoogle ScholarPubMed
34. Sata, F, Yamada, H, Suzuki, K, et al. . Functional maternal catechol-O-methyltransferase polymorphism and fetal growth restriction. Pharmacogenet Genomics. 2006; 16, 775–781.CrossRefGoogle ScholarPubMed
35. Christiansen, OB, Nybo Andersen, AM, Bosch, E, et al. . Evidence-based investigations and treatments of recurrent pregnancy loss. Fertil Steril. 2005; 83, 821–839.CrossRefGoogle ScholarPubMed
36. Rasch, V. Cigarette, alcohol, and caffeine consumption: risk factors for spontaneous abortion. Acta Obstet Gynecol Scand. 2003; 82, 182–188.CrossRefGoogle ScholarPubMed
37. Infante-Rivard, C, Fernandez, A, Gauthier, R, et al. . Fetal loss associated with caffeine intake before and during pregnancy. JAMA. 1993; 270, 2940–2943.CrossRefGoogle ScholarPubMed
38. Greenwood, DC, Alwan, N, Boylan, S, et al. . Caffeine intake during pregnancy, late miscarriage and stillbirth. Eur J Epidemiol. 2010; 25, 275–280.CrossRefGoogle ScholarPubMed
39. Stefanidou, EM, Caramellino, L, Patriarca, A, Menato, G. Maternal caffeine consumption and sine causa recurrent miscarriage. Eur J Obstet Gynecol Reprod Biol. 2011; 158, 220–224.CrossRefGoogle ScholarPubMed
40. Sata, F, Yamada, H, Suzuki, K, et al. . Caffeine intake, CYP1A2 polymorphism and the risk of recurrent pregnancy loss. Mol Hum Reprod. 2005; 11, 357–360.CrossRefGoogle ScholarPubMed
41. Scholl, TO, Johnson, WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr. 2000; 71(Suppl 5), 1295S–1303S.CrossRefGoogle ScholarPubMed
42. Makino, A, Nakanishi, T, Sugiura-Ogasawara, M, et al. . No association of C677T methylenetetrahydrofolate reductase and an endothelial nitric oxide synthase polymorphism with recurrent pregnancy loss. Am J Reprod Immunol. 2004; 52, 60–66.CrossRefGoogle Scholar
43. Kobashi, G, Kato, EH, Morikawa, M, et al. . MTHFR C677T polymorphism and factor V Leiden mutation are not associated with recurrent spontaneous abortion of unexplained etiology in Japanese women. Semin Thromb Hemost. 2005; 31, 266–271.CrossRefGoogle Scholar
44. Hohlagschwandtner, M, Unfried, G, Heinze, G, et al. . Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage. Fertil Steril. 2003; 79, 1141–1148.CrossRefGoogle ScholarPubMed
45. Kim, NK, Choi, YK, Kang, MS, et al. . Influence of combined methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase enhancer region (TSER) polymorphisms to plasma homocysteine levels in Korean patients with recurrent spontaneous abortion. Thromb Res. 2006; 117, 653–658.CrossRefGoogle ScholarPubMed
46. Barbosa, PR, Stabler, SP, Machado, AL, et al. . Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women. Eur J Clin Nutr. 2008; 62, 1010–1021.CrossRefGoogle ScholarPubMed
47. Nelen, WL, Blom, HJ, Thomas, CM, et al. . Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folate concentrations resulting from low dose folic acid supplementation in women with unexplained recurrent miscarriages. J Nutr. 1998; 128, 1336–1341.CrossRefGoogle ScholarPubMed
48. Christiansen, OB, Steffensen, R, Nielsen, HS, Varming, K. Multifactorial etiology of recurrent miscarriage and its scientific and clinical implications. Gynecol Obstet Invest. 2008; 66, 257–267.CrossRefGoogle ScholarPubMed
49. Khoury, MJ, Bertram, L, Boffetta, P, et al. . Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases. Am J Epidemiol. 2009; 170, 269–279.CrossRefGoogle ScholarPubMed
50. Wang, L, Wang, ZC, Xie, C, Liu, XF, Yang, MS. Genome-wide screening for risk loci of idiopathic recurrent miscarriage in a Han Chinese population: a pilot study. Reprod Sci. 2010; 17, 578–584.CrossRefGoogle Scholar
51. Kolte, AM, Nielsen, HS, Moltke, I, et al. . A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage. Mol Hum Reprod. 2011; 17, 379–385.CrossRefGoogle ScholarPubMed