Polymorphisms of methylenetetrahydrofolate reductase ( MTHFR ), methionine synthase ( MTR ), methionine synthase reductase ( MTRR ), and thymidylate synthase ( TYMS ) in multiple myeloma risk

• Published in: Leukemia research Vol. 32; no. 3; pp. 401 - 405
• Main Authors: Lima, Carmen S.P, Ortega, Manoela M, Ozelo, Margareth C, Araujo, Renato C, De Souza, Cármino A, Lorand-Metze, Irene, Annichino-Bizzacchi, Joyce M, Costa, Fernando F
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2008
• Subjects: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics; Aged; Female; Ferredoxin-NADP Reductase - genetics; Gene Frequency; Genetic Predisposition to Disease; Hematology, Oncology and Palliative Medicine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; MTHFR gene; MTR gene; MTRR gene; Multiple myeloma; Multiple Myeloma - genetics; Polymorphism, Genetic; Risk Factors; Susceptibility; Thymidylate Synthase - genetics; TYMS gene; TYMS gene; MTRR gene; MTHFR gene; MTR gene; Susceptibility; Multiple myeloma
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2007.06.001

Abstract We tested whether the polymorphisms of the methylenetetrahydrofolate reductase gene, MTHFR C677T and A1298C, the methionine synthase gene, MTR A2756G, the methionine synthase reductase gene, MTRR A66G, and the thymidylate synthase gene, TYMS 2R → 3R, involved in folate and methionine metabolism, altered the risk for multiple myeloma (MM). Genomic DNA from 123 MM patients and 188 controls was analysed by polymerase chain reaction and restriction digestion for the polymorphism analyses. The frequency of the MTR 2756 AG plus GG genotype was higher in patients than in controls (39.8% versus 23.4%, P = 0.001). Individual carriers of the variant allele G had a 2.31 (95% CI: 1.38–3.87)-fold increased risk for MM compared with others. In contrast, similar frequencies of the MTHFR , the MTRR and the TYMS genotypes were seen in patients and controls. These results suggest, for the first time, a role for the MTR A2756G polymorphism in MM risk in our country, but should be confirmed by large-scale epidemiological studies with patients and controls age matched.