Background: Several polymorphisms of the methylene-tetrahydrofolate reductase (MTHFR) gene have been described about decreased enzyme activity and hyperhomocysteinaemia in general population and about methotrexate treatment in patients with rheumatoid arthritis. Methotrexate (MTX) is the most widely prescribed drug for the treatment of rheumatoid arthritis (RA), and a number of evidence suggest that its efficacy and effects are dependent on genetic variants in genes of folate metabolism. Little, however, is known about the role that folate gene polymorphisms might have in the etiology of RA. Objectives: To examine the polymorphisms of MTHFR gene in a population of rheumatoid arthritis patients compared to healthy control matched for age and sex. Methods: A group of 157 consecutive RA patients (33 M and 125 F, middle age 58.1, range 30-89) has been studied for two common polymorphisms in the MTHFR gene, c.677C>T and c.1298A>C, that have been reported to be associated with altered MTHFR enzyme activity. All patients met the American College of Rheumatology revised criteria for rheumatoid arthritis. RA cases genotypes have been compared with a matched (sex and age) healthy control group. Results: Genotype frequencies of the c.677C>T polymorphism were similar in RA patients and in healthy subjects. c.677TT homozygotes were 19.7% in cases and 21.0% in controls. However, the frequency of c.1298CC homozygotes was found markedly increased in the RA patients group (12.1%) compared to controls (5.0%), giving a significant odd ratio of 2.62 (95% confidence interval 1.24-5.58). Conclusion: In the last yeas several studies have shown the predominant role of genetics, HLA-DRB1*0101, DRB1*0404, and DRB1*0405 of locus DRB1 (shared epitope, SE) as risk factor for rheumatoid arthritis. Our data suggest that the c.1298CC homozygosity in the MTHFR gene may be considered as a moderate risk factor for RA and point out a possible role of folate metabolism in the etiology of RA.
Association between MTHFR C.1298A > C polymorphism in the methylene-tetrahydrofolate (MTHFR) gene and increased risk for rheumatoid arthritis
RUBINI, Michele;PADOVAN, Melissa;BARICORDI, Olavio;CARTURAN, Sabrina;CAVALLARO, Alessandra;MASSARA, Alfonso;FOTINIDI, Maria;GOVONI, Marcello;TROTTA, Francesco
2005
Abstract
Background: Several polymorphisms of the methylene-tetrahydrofolate reductase (MTHFR) gene have been described about decreased enzyme activity and hyperhomocysteinaemia in general population and about methotrexate treatment in patients with rheumatoid arthritis. Methotrexate (MTX) is the most widely prescribed drug for the treatment of rheumatoid arthritis (RA), and a number of evidence suggest that its efficacy and effects are dependent on genetic variants in genes of folate metabolism. Little, however, is known about the role that folate gene polymorphisms might have in the etiology of RA. Objectives: To examine the polymorphisms of MTHFR gene in a population of rheumatoid arthritis patients compared to healthy control matched for age and sex. Methods: A group of 157 consecutive RA patients (33 M and 125 F, middle age 58.1, range 30-89) has been studied for two common polymorphisms in the MTHFR gene, c.677C>T and c.1298A>C, that have been reported to be associated with altered MTHFR enzyme activity. All patients met the American College of Rheumatology revised criteria for rheumatoid arthritis. RA cases genotypes have been compared with a matched (sex and age) healthy control group. Results: Genotype frequencies of the c.677C>T polymorphism were similar in RA patients and in healthy subjects. c.677TT homozygotes were 19.7% in cases and 21.0% in controls. However, the frequency of c.1298CC homozygotes was found markedly increased in the RA patients group (12.1%) compared to controls (5.0%), giving a significant odd ratio of 2.62 (95% confidence interval 1.24-5.58). Conclusion: In the last yeas several studies have shown the predominant role of genetics, HLA-DRB1*0101, DRB1*0404, and DRB1*0405 of locus DRB1 (shared epitope, SE) as risk factor for rheumatoid arthritis. Our data suggest that the c.1298CC homozygosity in the MTHFR gene may be considered as a moderate risk factor for RA and point out a possible role of folate metabolism in the etiology of RA.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
