medigraphic.com
ISSN 0187-5337 (Print)
Instituto Nacional de Perinatología

2006, Number 1-3

<< Back

Perinatol Reprod Hum 2006; 20 (1-3)

Significance of enviromental and genetic factors related to congenital heart diseases: MTHFR enzyme case

Sánchez-Urbina R, Galaviz-Hernández C, Sierra-Ramírez A, Morán-Barroso VF, García-Cavazos R

Language: Spanish
References: 49
Page: 39-47
PDF size: 124.73 Kb.


ABSTRACT

Congenital heart diseases (CHD) represent the third and sixth cause of death for children of less than a year and three years old respectively in Mexico. There is a very high degree of heterogeneity for CHD, having most of them multifactorial inheritance. CHD and neural tube defects (NTD) are the most common entities with this type of inheritance. It has been recognized that poor folic acid intake and the presence of C677T polymorphism on the MTHFR gene are both important environmental and genetic factors related to NTD development, through the rise of circulating blood homocysteine levels. Based on the close embryonic relationship at some processes between cardiac and neural tube development, it is thought that MTHFR enzyme could be actively involved on CHD development. Furthermore, different studies have demonstrated that there is a 24% risk reduction for CHD development when multivitamin intake schedule is followed even on the presence of C677T MTHFR polymorphism. At the same time, rises on homocysteine concentrations in mothers of patients affected by CHD, have been noticed in amniotic fluid as well as maternal plasma. Experimental Biology studies show that rises on homocysteine levels have a teratogenic effect producing NTD, CHD and some other malformative events. This paper, review how information regarding the possible relation between C677T MTHFR polymorphism, homocysteine levels and CHD development, in an attempt to esta-blish possible preventive measures for CC through folic acid intake.


REFERENCES

  1. Hoffman JIE. Incidence of congenital heart disease: II. Prenatal incidence. Pediatr Cardiol 1995; 15: 155-65.

  2. Mitchell SC, Korones SB Berendes HW, Congenital heart disease in 56,109 Births incidence and Natural History. Circulation 1971; XLIII: 323-32.

  3. Hoffman JIE, Chistianson R, Congenital Heart Disease in a cohort of 19, 502 births with long-term follow-up. Am J Cardiol 1978; 42: 641-7.

  4. Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW, Herpner SI, Downing JW. Congenital Heart Disease: prevalence at live birth. Am J Epidemiol 1985; 121: 31-6.

  5. Loffredo CA. Epidemiology of cardiovascular malformations: prevalence and risk factors. Am J Med Genet 2000; 97: 319-25.

  6. Dirección General de Información en Salud, Secretaría de Salud. Mortalidad preescolar. Boletín Médico del Hospital Infantil de México 2005; 62: 69-82.

  7. Ferencz C, Neill CA, Boughman JA, Rubin JD, Brenner JI, Perry LW. Congenital cardiovascular malformations associated with chromosome abnormalities: an epidemiologic study. J Pediatr 1989; 114: 79-86.

  8. Johnson MC, Hing A, Wood MK, Watson MS. Chromosome abnormalities in congenital heart disease. Am J Med Genet 1997; 70: 292-8.

  9. Maeda JH, Yamagishi H, Matsuoka R, Ishihara J, Tokumura M, Fukushima H, et al. Frequent Association of 22q11.2 Deletion With Tetralogy of Fallot. Am J Med Genet 2000; 92: 269-72.

  10. Marino B, Digilio MC, Grazioli S, Formiagari R, Mingarelli R, Giannotti A, Dallapiccola B. Associated cardiac anomalies in isolated and sindromic patients with tetralogy of fallot. Am J Cardiol 1996; 77: 505-8.

  11. Melchionda S, Digilio MC, Mingarelli R, Novelli G, Scambler P, Marino B, et al. Transposition of the great arteries associated with deletion of chromosome 22q11. Am J Cardiol 1995; 75: 95-8.

  12. Goldmuntz E, Clark BJ, Mitchell LE, Jawad A.F, Cuneo BF, Reed L, et al. Frecuency of 22q11 Deletions in patients with conotruncal defects. Pediatr Cardiol 1998; 32: 492-8.

  13. Van der Put NMJ, Gabreëls F, Stevens EMB, Smeitinik JAM, Trjbels FJM, Eskes TKA, et al. Am J Hum Genet 1998; 62: 1044-51.

  14. Frosst P, Blom H, Milos R. Identification of a candidate genetic risk factor for vascular disease: a common mutation in methylente-trahydrofolate reductase. Nat Genet 1995; 10:111-3.

  15. Nussbaumr RL, Mc Inees RR, Willard HF. Thompson & Thompson Genetics in Medicine. 6th Ed. Edit. Saunders; 2001, p. 304-10.

  16. Relton CL, Wilding CS, Pearce MS Laffing AJ, Jonas PA, Lynch SA, Tawn EJ, Burn J. Gene-gene interaction in folate-related genes and risk of neural tube defects in a UK population. J Med Genet 2004; 41: 256-60.

  17. Boyles AL, Hammock P, Speer MC. Candidate gene analysis in human neural tube defects. Am J Med Genet (Semin Med Genet) 2005; 135C: 9-23.

  18. Goyette P, Sumner JS, Milos R, Duncan AMV, Rosenblatt DS, Matthews RG, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet 1994; 7: 195-200.

  19. Guéant-Rodriguez RM, Guéant JL, Debard R, Thirion S, Hong LX, Bronowicki JP, et al. Prevalence of methylenetetrahydrofolate reductase 6777T and 1298C alleles and folate status: a comparative study in Mexican, West African, and European populations. Am J Clin Nutr 2006; 83: 701-7.

  20. Botto LD. 5, 10-methylenetetrahydrofolate reductase gene variants and congenital anomalies. AhuGE Review. Am J Epidemiol 2000; 151: 862-77.

  21. Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M, et al. Geographical and ethnic variation of the 677C > T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet 2003; 40: 619-25.

  22. Disponible en: www.ncbi.nlm.nih.gov

  23. Van der Put NMJ, Gabreëls F, Stevens EMB, Smeitink JAM, Trijbels FJM, Eskes TKA, van den Heuvel LP, Blom HJ. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 1998; 62: 1044-51.

  24. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R, Congenital heart defects and maternal derangement of homocysteine metabolism. Mol Genet Metab 1998, 64(3): 169-72.

  25. Scriver CR, Beaudet AL, William SS, Valle D. The Metabolic & Molecular Bases Inherited Disease. 8th Ed. McGraw-Hill; 2001, p. 3897-933.

  26. Davalos RIP, Olivares P, Castillo MT, Cantú JM, Ibarra B, Moran MC, et al. The C677T polimorphism of the methylenetetra-hydrofolate reductase gene in Mexican mestizo neural-tube defect parents, control mestizo and native populations. Ann Genet 2002; 43: 89-92.

  27. Mutchinick OM, López MA, Luna L, Waxman J, Babinsky VE, RYVEMCE collaborative Group. Hig prevalence of the thermolabile metylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects. Mol Genet Metab 1999; 68: 461-7.

  28. González-Herrera L, García-Escalante G, Castillo-Zapata I, Canto-Herrera J, Pinto-Escalante D, Díaz-Rubio F, et al. Frecuency of thermolabile variant defects in the State of Yucatan, México. Clin Genet 2002; 62: 394-8.

  29. Fonseca V, Guuba SC, Fink LM, Hyper-homocysteinemia and the endocrine system: implications for atherosclerosis and trombosis. Endocr Rev 1999; 20: 738-59.

  30. Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999; 19: 217-46.

  31. Aubard Y, Darodes N, Cantaloube M, Hyperhomocysteinemia and pregnancy-review of our pre understanding and therapeutic implications, European. J Gynecol Obstet Biol Reprod 2000; 93: 157-65.

  32. Wenstrom KD, Johanning GL, Johnston KE, Dubard M. Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malfomations. Am J Obstet Gynecol 2001; 184: 806-17.

  33. Medina MA, Urdiales JL, Amores-Sánchez MI. Role of homocysteine in cell metabolism. Eur J Biochem 2001; 268: 3871-82.

  34. Ek J, Magnus EM. Plasma and red blood cell folate during normal pregnancies. Acta Obstet Gynecol Scand 1981; 60: 247-51.

  35. Malinow MR, Rajkovic A, Duell PB, Hess DL, Upson BM. The relationship between maternal and neonatal umbilical cord plasma homocyst(e)ine suggest a potential role for a maternal homocyst(e)ine in fetal metabolism. Am J Obstet Gynecol 1998; 178: 228-33.

  36. Molloy AM, Mills JL, McPartlin J, Kirke PN, Scott JM, Daly S. Maternal and fetal plasma homocysteine concentrations at birth: the influence of folate, vitamin B12, and the 5,10-methylenetetrahydrofolate reductase 677C® T variant. Am J Obstet Gynecol 2002; 186: 499-503.

  37. Bonnette RE, Caudill MA, Boddie AM, Hutson AD, Kauwell GPA, Bailey LB. Plasma homocyst(e)ine concentrations in pregnant and nonpregnant women with controlled folate intake. Obstet Gynecol 1998; 92: 167-70.

  38. Walker MC, Smith GN, Perkins SL, Keelv EJ, Garner PR. Changes in homocysteine levels during normal pregnancy. Am J Obstet Gynecol 1999; 180: 360-4.

  39. Daly SF, Molloy AM, Millis JL, Lee YJ, Conley M, Kirke PN, et al. The influence of 5,10 methylenetetrahydrofolate reductase genotypes on enzyme activity in placental tissue. Br J Obstet Gynecol 1999; 106: 1214-8.

  40. Botto LD, Khoury MJ, Mulinare J, Erickson JD. Periconceptional multivitamin use and the ocurrence of conotruncal heart defects: results from a population-based, case-control study. Pediatrics 1996; 98: 911-7.

  41. Czeizel AE. Prevention of congenital abnormalities by periconceptional multivitamin supplementation. Br Med J 1993; 306: 1645-8.

  42. Kapusta L, Haagmans MLM, Steegers EAP, Cuypers MHM, Blom HJ, Eskes TKAB. J Pediatr 1999; 135: 773-4.

  43. Junker R, Kotthoff S, Heintich V, Halimeh S, Kosch A, Koch HG, et al. Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factor for congenital heart disease. Cardiovasc Res 2001; 51: 251-4.

  44. Rosenquist TH, Tatashak S A, Selhub J. Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acid. Proc Natl Acad Sci 1996; 93: 1527-32.

  45. Rosenquist TH, Schneider AM, Monachan DT. N-methyl-D-aspartate receptor agonists modulate homocysteine-induced developmental abnormalities. FASEB J 1999; 13: 1523-31.

  46. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, et al. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 1992; 256: 1217-21.

  47. Goodman & Guillman A. Bases farmacoló-gicas de la terapéutica. 10a. ed. Ed. Mc Graw Hill, Interamericana; 2003.

  48. Komuro H, Rakic P. Modulation of neural migration by NMDA receptors. Science 1993; 260: 95-7.

  49. Andaloro VJ, Monaghan DT, Rosenquist TH. Dextromethorphan and Other N-Methyl-D-Aspartate Receptor Antagonists are teratogenic in the avian embryo model. Pediatr Res 1998; 43: 1-7.




2020     |     www.medigraphic.com