Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts

American Journal of Medical Genetics, Part A

Volumn 146, Issue 4, 2008, Pages 440-449

  Boyles, Abee L ^a   Wilcox, Allen J ^a   Taylor, Jack A ^a   Meyer, Klaus ^b   Fredriksen, Åse ^b   Ueland, Per Magne ^b   Drevon, Christian A ^c   Vollset, Stein Emil ^b   Lie, Rolv Terje ^b  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^b UNIVERSITY OF BERGEN   (Norway)

^c UNIVERSITY OF OSLO   (Norway)

Author keywords

Alleles; Cleft lip; Cleft palate; Dietary supplements; Folic acid; Humans; Metabolism; Single nucleotide polymorphisms

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); CARBON; CYSTATHIONINE BETA SYNTHASE; FOLIC ACID;

ARTICLE; CARBON METABOLISM; CLEFT FACE; CLEFT LIP; CLEFT PALATE; DIET SUPPLEMENTATION; DNA POLYMORPHISM; FOLATE METABOLISM; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HUMAN; MAJOR CLINICAL STUDY; MOLECULAR INTERACTION; NEURAL TUBE DEFECT; NEWBORN; NORWAY; POPULATION RESEARCH; PRENATAL CARE; PRIORITY JOURNAL; RISK ASSESSMENT;

CARBON; CASE-CONTROL STUDIES; CLEFT LIP; CLEFT PALATE; DIETARY SUPPLEMENTS; FEMALE; FOLIC ACID; GENE FREQUENCY; HUMANS; INFANT, NEWBORN; MALE; METABOLIC NETWORKS AND PATHWAYS; MODELS, BIOLOGICAL; POLYMORPHISM, GENETIC; PREGNANCY;

EID: 38849187271     PISSN: 15524825     EISSN: 15524833     Source Type: Journal    
DOI: 10.1002/ajmg.a.32162     Document Type: Article

References (70)

1. Aras O, Hanson NQ, Yang F, Tsai MY. 2000. Influence of 699C->T and 1080C->T polymorphisms of the cystathionine beta-synthase gene on plasma homocysteine levels. Clin Genet 58:455-459.
2. Badovinac RL, Werler MM, Williams PL, Kelsey KT, Hayes C. 2007. Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: A meta-analysis. Birth Defects Res A Clin Mol Teratol 79:8-15.
3. Beaty TH, Hetmanski JB, Zeiger JS, Fan YT, Liang KY, VanderKolk CA, McIntosh I. 2002. Testing candidate genes for non-syndromic oral clefts using a case-parent trio design. Genet Epidemiol 22:1-11.
4. Bennouar N, Allami A, Azeddoug H, Bendris A, Laraqui A, El Jaffali A, El Kadiri N, Benzidia R, Benomar A, Fellat S, Benomar M. 2007. Thermolabile methylenetetrahydrofolate reductase C677T polymorphism and homocysteine are risk factors for coronary artery disease in moroccan population. J Biomed Biotechnol 1:80687.
5. Berry A. 1998. Focusing on folic acid. Task force organizing to promote consumption of folic acid. AWHONN Lifelines 2:19-19-20.
6. Blanton SH, Kolle BS, Hecht JT, Mulliken JB, Martin ER. 2000. No evidence supporting MTHFR as a risk factor in the development of familial NSCLP. Am J Med Genet 92:370-371.
7. Botto LD, Moore CA, Khoury MJ, Erickson JD. 1999. Neural-tube defects. N Engl J Med 341:1509-1519.
8. Boyles AL, Billups AV, Deak KL, Siegel DG, Mehltretter L, Slifer SH, Bassuk AG, Kessler JA, Reed MC, Nijhout HF, George TM, Enterline DS, Gilbert JR, Speer MC. 2006. Neural tube defects and folate pathway genes: Family-based association tests of gene-gene and gene-environment interactions. Environ Health Perspect 114:1547-1552.
9. Brockton NT. 2006. Localized depletion: The key to colorectal cancer risk mediated by MTHFR genotype and folate? Cancer Causes Control 17:1005-1016.
10. Chen J, Giovannucci E, Kelsey K, Rimm EB, Stampfer MJ, Colditz GA, Spiegelman D, Willett WC, Hunter DJ. 1996. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res 56:4862-4864.
11. Chevrier C, Perret C, Bahuau M, Zhu H, Nelva A, Herman C, Francannet C, Robert-Gnansia E, Finnell RH, Cordier S. 2007. Fetal and maternal MTHFR C677T genotype, maternal folate intake and the risk of nonsyndromic oral clefts. Am J Med Genet Part A 143A:248-257.
12. de Franchis R, Buoninconti A, Mandato C, Pepe A, Sperandeo MP, Del Gado R, Capra V, Salvaggio E, Andria G, Mastroiacovo P. 1998. The C677T mutation of the 5,10-methylenetetrahydrofolate reductase gene is a moderate risk factor for spina bifida in Italy. J Med Genet 35:1009-1013.
13. Finkelstein JD. 1990. Methionine metabolism in mammals. J Nutr Biochem 1:228-237.
14. Fredriksen A, Meyer K, Ueland PM, Vollset SE, Grotmol T, Schneede J. 2007. Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism. Hum Mutat 28:856-865.
15. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, et al. 1995. A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111-113.
16. Caspar DA, Matioli SR, de Cassia Pavanello R, Araujo BC, Alonso N, Wyszynski D, Passos-Bueno MR. 2004. Maternal MTHFR interacts with the offspring's BCL3 genotypes, but not with TGFA, in increasing risk to nonsyndromic cleft lip with or without cleft palate. Eur J Hum Genet 12:521-526.
17. Grunert RR, Braune A, Schnackenberg E, Schloot W, Krause HR. 2002. Genetic differences in enzymes of folic acid metabolism in patients with lip-jaw-palate clefts and their relatives. Mund Kiefer Gesichtschir 6:131-133.
18. Hayes C, Werler MM, Willett WC, Mitchell AA. 1996. Case-control study of periconceptional folic acid supplementation and oral clefts. Am J Epidemiol 143:1229-1234.
19. Itikala PR, Watkins ML, Mulinare J, Moore CA, Liu Y. 2001. Maternal multivitamin use and orofacial clefts in offspring. Teratology 63:79-86.
20. Jakubowski H, Zhang L, Bardeguez A, Aviv A. 2000. Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: Implications for atherosclerosis. Circ Res 87:45-51.
21. Jiang Q, Chen K, Ma X, Li Q, Yu W, Shu G, Yao K. 2005. Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer. Cancer Detect Prev 29:146-154.
22. Jugessur A, Wilcox AJ, Lie RT, Murray JC, Taylor JA, Ulvik A, Drevon CA, Vindenes HA, Abyholm FE. 2003. Exploring the effects of methylenetetrahydrofolate reductase gene variants C677T and A1298C on the risk of orofacial clefts in 261 Norwegian case-parent triads. Am J Epidemiol 157:1083-1091.
23. Krapels IP, Vermeij-Keers C, Muller M, de Klein A, Steegers-Theunissen RP. 2006. Nutrition and genes in the development of orofacial clefting. Nutr Rev 64:280-288.
24. Le Marchand L, Donlon T, Hankin JH, Kolonel LN, Wilkens LR, Seifried A. 2002. B-vitamin intake, metabolic genes, and colorectal cancer risk (United States). Cancer Causes Control 13:239-248.
25. Le Marchand L, Wilkens LR, Kolonel LN, Henderson BE. 2005. The MTHFR C677T polymorphism and colorectal cancer: The multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 14:1198-1203.
26. Lidral AC, Moreno LM. 2005. Progress toward discerning the genetics of cleft lip. Curr Opin Pediatr 17:731-739.
27. Lin PI, Vance JM, Pericak-Vance MA, Martin ER. 2007. No gene is an island: The flip-flop phenomenon. Am J Hum Genet 80:531-538.
28. Ma J, Stampfer MJ, Christensen B, Giovannucci E, Hunter DJ, Chen J, Willett WC, Selhub J, Hennekens CH, Gravel R, Rozen R. 1999. A polymorphism of the methionine synthase gene: Association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 8:825-829.
29. Marazita ML, Spence MA, Melnick M. 1984. Genetic analysis of cleft lip with or without cleft palate in Danish kindreds. Am J Med Genet 19:9-18.
30. Martinelli M, Scapoli L, Pezzetti F, Carinci F, Carinci P, Stabellini G, Bisceglia L, Gombos F, Tognon M. 2001. C677T variant form at the MTHFR gene and CL/P: A risk factor for mothers? Am J Med Genet 98:357-360.
31. Martinelli M, Scapoli L, Palmieri A, Pezzetti F, Baciliero U, Padula E, Carinci P, Morselli PG, Carinci F. 2006. Study of four genes belonging to the folate pathway: Transcobalamin 2 is involved in the onset of non-syndromic cleft lip with or without cleft palate. Hum Mutat 27:294.
32. Meyer K, Fredriksen A, Ueland PM. 2004. High-level multiplex genotyping of polymorphisms involved in folate or homocysteine metabolism by matrix-assisted laser desorption/ionization mass spectrometry. Clin Chem 50:391-402.
33. Mills JL, Kirke PN, Molloy AM, Burke H, Conley MR, Lee YJ, Mayne PD, Weir DG, Scott JM. 1999. Methylenetetrahydrofolate reductase thermolabile variant and oral clefts. Am J Med Genet 86:71-74.
34. Morrison K, Papapetrou C, Hol FA, Mariman EC, Lynch SA, Burn J, Edwards YH. 1998. Susceptibility to spina bifida: An association study of five candidate genes. Ann Hum Genet 62:379-396.
35. Mostowska A, Hozyasz KK, Jagodzinski PP. 2006. Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population. Clin Genet 69:512-517.
36. MRC Vitamin Study Research Group. 1991. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 338:131-137.
37. Mukhopadhyay N, Almasy L, Schroeder M, Mulvihill WP, Weeks DE. 2005. Mega2: Data-handling for facilitating genetic linkage and association analyses. Bioinformatics 21:2556-2557.
38. Munger RG. 2002. Maternal nutrition and oral clefts. In: Wyszynski DF, editor. Cleft lip and palate: From origin to treatment. Oxford: Oxford University Press. p 170-192.
39. Munger RG, Sauberlich HE, Corcoran C, Nepomuceno B, Daack-Hirsch S, Solon FS. 2004. Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in the Philippines. Birth Defects Res A Clin Mol Teratol 70:464-471.
40. Munoz JB, Lacasana M, Cavazos RG, Borja-Aburto VH, Galaviz-Hernandez C, Garduno CA. 2007. Methylenetetrahydrofolate reductase gene polymorphisms and the risk of anencephaly in Mexico. Mol Hum Reprod 13:419-424.
41. Nurk E, Tell GS, Refsum H, Ueland PM, Vollset SE. 2004. Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: The Hordaland Homocysteine Study. Am J Med 117:26-31.
42. O'Leary VB, Mills JL, Parle-McDermott A, Pangilinan F, Molloy AM, Cox C, Weiler A, Conley M, Kirke PN, Scott JM, Brody LC. 2005. Screening for new MTHFR polymorphisms and NTD risk. Am J Med Genet Part A 138A:99-106.
43. Pei L, Zhu H, Zhu J, Ren A, Finnell RH, Li Z. 2006. Genetic variation of infant reduced folate carrier (A80G) and risk of orofacial defects and congenital heart defects in China. Ann Epidemiol 16:352-356.
44. Pezzetti F, Martinelli M, Scapoli L, Carinci F, Palmieri A, Marchesini J, Carinci P, Caramelli E, Rullo R, Gombos F, Tognon M. 2004. Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate. Hum Mutat 24:104-105.
45. Prescott NJ, Winter RM, Malcolm S. 2002. Maternal MTHFR genotype contributes to the risk of non-syndromic cleft lip and palate. J Med Genet 39:368-369.
46. Rampersaud E, Morris RW, Weinberg CR, Speer MC, Martin ER. 2007. Power calculations for likelihood ratio tests for offspring genotype risks, maternal effects, and parent-of-origin (POO) effects in the presence of missing parental genotypes when unaffected siblings are available. Genet Epidemiol 31:18-30.
47. Relton CL, Wilding CS, Jonas PA, Lynch SA, Tawn EJ, Burn J. 2003. Genetic susceptibility to neural tube defect pregnancy varies with offspring phenotype. Clin Genet 64:424-428.
48. Rubini M, Brusati R, Garattini G, Magnani C, Liviero F, Bianchi F, Tarantino E, Massei A, Pollastri S, Carturan S, Amadori A, Bertagnin E, Cavallaro A, Fabiano A, Franchella A, Calzolari E. 2005. Cystathionine beta-synthase c.844ins68 gene variant and non-syndromic cleft lip and palate. Am J Med Genet Part A 136A:368-372.
49. Shaw GM, Lammer EJ, Wasserman CR, O'Malley CD, Tolarova MM. 1995. Risks of orofacial clefts in children born to women using multivitamins containing folic acid periconceptionally. Lancet 346:393-396.
50. Shaw GM, Rozen R, Finnell RH, Todoroff K, Lammer EJ. 1998. Infant C677T mutation in MTHFR, maternal periconceptional vitamin use, and cleft lip. Am J Med Genet 80:196-198.
51. Shaw GM, Zhu H, Lammer EJ, Yang W, Finnell RH. 2003. Genetic variation of infant reduced folate carrier (A80G) and risk of orofacial and conotruncal heart defects. Am J Epidemiol 158:747-752.
52. Shaw GM, Carmichael SL, Laurent C, Rasmussen SA. 2006. Maternal nutrient intakes and risk of orofacial clefts. Epidemiology 17:285-291.
53. Shi M, Caprau D, Dagle J, Christiansen L, Christensen K, Murray JC. 2004. Application of kinetic polymerase chain reaction and molecular beacon assays to pooled analyses and high-throughput genotyping for candidate genes. Birth Defects Res A Clin Mol Teratol 70:65-74.
54. Shotelersuk V, Ittiwut C, Siriwan P, Angspatt A. 2003. Maternal 677CT/1298AC genotype of the MTHFR gene as a risk factor for cleft lip. J Med Genet 40:e64.
55. Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M. 1999. Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol Biomarkers Prev 8:513-518.
56. Tang LS, Finnell RH. 2003. Neural and orofacial defects in Folp1 knockout mice [corrected]. Birth Defects Res A Clin Mol Teratol 67:209-218.
57. Tolarova MM, van Rooij IALM, Pastor M, van der Put NMJ, Goldberg AC, Hol F, Capozzi A, Thomas CMG, Paster L, Mosby T, Ferrari C, Eskes TKAB, Steegers-Theunissen RPM. 1998. A common mutation in the MTHFR gene is a risk factor for nonsyndromic cleft lip and palate anomalies [Abstract]. Am J Hum Genet 63:A27.
58. Ulvik A, Vollset SE, Hansen S, Gislefoss R, Jellum E, Ueland PM. 2004. Colorectal cancer and the methylenetetrahydrofolate reductase 677C -> T and methionine synthase 2756A -> G polymorphisms: A study of 2,168 case-control pairs from the JANUS cohort. Cancer Epidemiol Biomarkers Prev 13:2175-2180.
59. van der Linden IJ, Afman LA, Heil SG, Blom HJ. 2006. Genetic variation in genes of folate metabolism and neural-tube defect risk. Proc Nutr Soc 65:204-215.
60. van der Put NM, Steegers-Theunissen RP, Frosst P, Trijbels FJ, Eskes TK, van den Heuvel LP, Mariman EC, den Heyer M, Rozen R, Blom HJ. 1995. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 346:1070-1071.
61. van Rooij IA, Vermeij-Keers C, Kluijtmans LA, Ocke MC, Zielhuis GA, Goorhuis-Brouwer SM, van der Biezen JJ, Kuijpers-Jagtman AM, Steegers-Theunissen RP. 2003. Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate? Am J Epidemiol 157:583-591.
62. van Rooij IA, Ocke MC, Straatman H, Zielhuis GA, Merkus HM, Steegers-Theunissen RP. 2004. Periconceptional folate intake by supplement and food reduces the risk of non-syndromic cleft lip with or without cleft palate. Prev Med 39:689-694.
63. Verkleij-Hagoort A, Bliek J, Sayed-Tabatabaei F, Ursem N, Steegers E, Steegers-Theunissen R. 2007. Hyperhomocysteinemia and MTHFR polymorphisms in association with orofacial clefts and congenital heart defects: A meta-analysis. Am J Med Genet Part A 143A:952-960.
64. Vieira AR, Murray JC, Trembath D, Orioli IM, Castilla EE, Cooper ME, Marazita ML, Lennon-Graham F, Speer M. 2005. Studies of reduced folate carrier 1 (RFC1) A80G and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with neural tube and orofacial cleft defects. Am J Med Genet Part A 135A:220-223.
65. Weinberg CR, Wilcox AJ, Lie RT. 1998. A log-linear approach to case-parent-triad data: Assessing effects of disease genes that act either directly or through maternal effects and that may be subject to parental imprinting. Am J Hum Genet 62:969-978.
66. Werler MM, Hayes C, Louik C, Shapiro S, Mitchell AA. 1999. Multivitamin supplementation and risk of birth defects. Am J Epidemiol 150:675-682.
67. Wilcox AJ, Lie RT, Solvoll K, Taylor J, McConnaughey DR, Abyholm F, Vindenes H, Vollset SE, Drevon CA. 2007. Folic acid supplements and risk of facial clefts: National population based case-control study. BMJ 334:464-470.
68. Wong WY, Eskes TK, Kuijpers-Jagtman AM, Spauwen PH, Steegers EA, Thomas CM, Hamel BC, Blom HJ, Steegers-Theunissen RP. 1999. Nonsyndromic orofacial clefts: Association with maternal hyperhomocysteinemia. Teratology 60:253-257.
69. Zhu H, Curry S, Wen S, Wicker NJ, Shaw GM, Lammer EJ, Yang W, Jafarov T, Finnell RH. 2005. Are the betaine-homocysteine methyltransferase (BHMT and BHMT2) genes risk factors for spina bifida and orofacial clefts? Am J Med Genet Part A 135A:274-277.
70. Zhu J, Ren A, Hao L, Pei L, Liu J, Zhu H, Li S, Finnell RH, Li Z. 2006. Variable contribution of the MTHFR C677T polymorphism to non-syndromic cleft lip and palate risk in China. Am J Med Genet Part A 140A:551-557.