C677t (rs1801133 ) MTFHR gene polymorphism frequency in a colombian population
Abstract
Introduction:Abnormal levels of the enzyme methylenetetrahydrofolate reductase (MTHFR) are associated with an increased risk of both cardiovascular and cerebrovascular disease and higher concentrations of homocysteine. Abnormal levels are also related to birth defects, pregnancy complications, cancer and toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the enzyme. Genetic associations have been related to treatment efficacy.
Objective:To establish the frequency of the C> T polymorphism at nucleotide 677 of the MTHFR gene in a group of Colombian individuals.
Methods:Data from pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms were retrospectively collected (Pathway Genomics®). The frequency of the C> T MTHFR rs1801133 marker polymorphism was analyzed.
Results:Microarray data from 68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T were statistically significantly different (p= 0.00, p= 0.026, respectively), as were C/T and T / T (p= 0.0001).
Conclusions:Results for the C/C and C/T genotypes in a Colombian population are similar to other previously studied groups of healthy subjects. Subjects from our population might be at risk of developing diseases associated with MTHFR polymorphisms and might present toxicity and adverse effects if treated with MTX, which suggests the need to evaluate therapeutic alternatives based on individual pharmacogenetic studies.
Authors
Downloads
Keywords
- Methotrexate
- genotype
- alleles
- polymorphism
- metylentetrahidrofolate-reductase
References
Brinker R, Ranganathan P. Methotrexate pharmacogenetics in rheumatoid arthritis. Clin Exp Rheumatol. 2010; 28(5) 61:S33–S9.
Evans W, Relling MV. Pharmacogenomics: translating functional genomics international therapeutics. Science. 1999; 286: 487–91.
Evans EE, Mcleod HL. Pharmacogenomics drug disposition, drug targets, and side effects. N Engl J Med. 2003; 348: 538–49.
Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999; 340: 253–9.
Gubner R, August S, Ginsberg V. Therapeutic suppression of tissue reactivity. II. Effect of aminopterinin rheumatoid arthritis and psoriasis. Am J Med Sci. 1951; 221: 176–82.
Andersen PA, West SG, O'Dell JR, Via CS, Claypool RG, Kotzin BL. Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann Internal Med. 1985; 103: 489–96.
Kang, SS, Passen EL, Ruggie N, Wong PW, Sora H. Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease. Circulation. 1993; 88: 1463–9.
Tian H, Cronstein BN. Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis. Bull NYU Hosp Jt Dis. 2007; 65: 168–73.
Refsum H, Ueland PM, Nygård O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med. 1998; 49: 31–62.
Finnell, RH, Greer KA, Barber RC, Piedrahita JA. Neural tube and craniofacial defects with special emphasis on folate pathway genes. Crit Rev Oral Biol Med. 1998; 9: 38–53.
Ray, JG, Laskin CA. Folic acid and homocysteine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: a systematic review. Placenta. 1999; 20: 519–29.
Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a Huge Review. Am J Epidemiol. 2004; 159: 423–43.
Meshkin B, Blum K. Folate nutrigenetics: a convergence of dietary folate metabolism, folic acid supplementation, and folate antagonist pharmacogenetics. Drug Metab Lett. 2007; 1: 55–60.
Bailey LB, Gregory JF. Folate metabolism and requirements. J Nutr. 1999; 4: 779–82.
Sun L, Sun Y, Bo W, Cao H, Chen Y. Methylenetetrahydrofolate reductase polymorphisms and susceptibility to gastric cancer in Chinese populations: a meta-analysis. Eur J Cancer Prev. 2008; 17: 446–52.
Fisher MC, Cronstein BN. Meta-analysis of methylenetetrahydrofolate reductase (MTHFR) polymorphisms affecting methotrexate toxicity. J Rheumatol. 2009; 36: 539–45.
Kim SK, Jun JB, El-Sohemy A, Bae SC. Cost-effectiveness analysis of MTHFR polymorphism screening by polymerase chain reaction in Korean patients with rheumatoid arthritis receiving methotrexate. J Rheumatol. 2006; 33: 1266–74.
Taniguchi A, Urano W, Tanaka E, Furihata S, Kamitsuji S, Inoue E, et al. Validation of the associations between single nucleotide polymorphisms orhaplotypes and responses to disease-modifying anti rheumatic drugs in Patients with rheumatoid arthritis: a proposal for prospective pharmacogenomic study in clinical practice. Pharmacogenet Genomics. 2007; 17: 383–90.
van Ede AE, Laan RF, Blom HJ, Huizinga TW, Haagsma CJ, Giesendorf BA, et al. The C677T mutation in the methylenetetrahydrofolatereductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arthritis Rheum. 2001; 44: 2525–30.
Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G. Intermediate homocysteinemia: athermolabile variant of methylenetetrahydrofolate-reductase. Am J Hum Gen. 1988; 43: 414–21.
Delgado-Enciso I, Martínez-Garza S, Rojas-Martínez A, Espinosa-Gómez F, Canseco-Avila L, Vidal-Gutiérrez O et al Interacciones entre polimorfismos del gen MTHFR, gestaciones e inicio de vida sexual modifican el riesgo para cáncer cérvico-uterino en una población del noroeste de México. Rev Invest Clín. 2006; 58: 462–9.
Bermúdez M, Briceño I, Gil F, Bernal J. Homocisteína y polimorfismos de cistationinasintasa y metilentetrahidrofolato reductasa en población sana de Colombia. Colomb Med. 2006; 37: 46–52.
García-Robles R, Ayala-Ramírez PA, Villegas VE, Salazar M, Bernal J, et al. Estudio del polimorfismo MTHFR C677T en recién nacidos con cardiopatías congénitas aisladas, en una población colombiana. Univ Méd. 2011; 52: 269–77.
Torres JD, Cardona H, Alvarez L, Cardona-Maya W, Castañeda SA, et al. Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population. Am J Hematol. 2006; 81: 933–7.
Cardona H, Cardona-Maya W, Gómez JG, Castañeda SJ, Gómez M, Bedoya G. Relacio´n entre los polimorfismos de la metilen-tetrahidrofolato-reductasa y los niveles de homocistei´na en mujeres con pe´rdida gestacional recurrente: perspectiva desde la nutrigene´tica. Nutrición Hospitalaria. 2008; 23: 277–82.
González-Galofre Z, Villegas V, Martínez-Agüero M. Determinación del polimorfismo C677T de metilentetrahidrofolato reductasa (MTHFR) en una población piloto de estudiantes de la Universidad del Rosario. Rev Cienc Salud. 2010; 8(1): 7–21.
Baum L, Wong KS, Ng HK, Tomlinson B, Rainer TH, Chan DK, et al. Methylenetetrahydrofolate reductase gene A222V polymorphism and risk of ischemic stroke. Clin Chem Lab Med. 2004; 42: 1370–6.
Stolzenberg-Solomon RZ, Qiao YL, Abnet CC, Ratnasinghe DL, Dawsey SM, Dong ZW, et al. Esophageal and gastric cardia cancer risk and folate- and vitamin B12-related polymorphisms in Linxian, China. Cancer Epidemiol Biomarkers Prev. 2003; 12: 1222–6.
Li DH, Ahmed M, Li YN, Jiao L, Chou TH, Wolff RA, et al. 5,10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14: 1470–6.
Alluri RV, Mohan V, Komandur S, Chawda K, Chaudhuri JR, Hasan Q. MTHFR C677T gene mutation as a risk factor for arterial stroke: A hospital based study. Eur J Neurol. 2005; 12: 40–4.
Wang LD, Guo RF, Fan ZM, He X, Gao SS, Guo HQ, et al. Association of methylenetetrahydrofolate reductase and thymidylate synthase promoter polymorphisms with genetic susceptibility to esophageal and cardia cancer in a Chinese high-risk population. Dis Esophagus. 2005; 18: 177–84.
Meadows DN, Pyzik M, Wu Q, Torre S, Gros P, Vidal SM, Rozen R. Increased resistance to malaria in mice with methylenetetrahydrofolate reductase (MTHFR) deficiency suggests a mechanism for selection of the MTHFR 677C>T (c.6665C>T) variant. Hum Mutat. 2014; 35(5): 594–600.
Fodil-Cornu N, Kozij N, Wu Q, Rozen R, Vidal SM . Methylenetetrahydrofolate reductase (MTHFR) deficiency enhances resistance against cytomegalovirus infection. Genes Immun. 2009; 10: 662–6.
Semmler A, Moskau S, Lutz H, Meyer P, Linnebank M. Haplotype analysis of the 5,10-methylenetetrahydrofolate reductase (MTHFR) c.11298A>C (E429A) polymorphism. BMC Res Notes. 2011; 4: 439–9.
Copyright (c) 2015 Universidad del Valle
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The copy rights of the articles published in Colombia Médica belong to the Universidad del Valle. The contents of the articles that appear in the Journal are exclusively the responsibility of the authors and do not necessarily reflect the opinions of the Editorial Committee of the Journal. It is allowed to reproduce the material published in Colombia Médica without prior authorization for non-commercial use
