Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation that causes joint deformity, pain, functional limitations and psychological distress leading to work disability and consequent relevant social and individual costs. RA is a complex disease that results from the interplay between genetic and environmental factors. Identification of the genetic factors involved in the pathogenesis of RA could be crucial for early diagnosis and development of treatment strategies directed at the cause of the disease. However, still little is known susceptibility genes for RA. Although HLA-DRB1 is the main RA gene, it accounts for only part of the genetic risk for RA. Association studies suggested that other genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22 play a role in the etiology of the disease. Metotrexate (MTX) is the first line treatment for RA and its efficacy has been reported to be dependent on gene variant in the Methylenetetrahydrofolate Reductase (MTHFR) gene. To assess the possible role of MTHFR polymorphisms in the etiology of RA, we genotyped the c.677C>T and the c.1298A>C variant in MTHFR gene in a group of 217 Italian RA patients and in a matched group of healthy controls. While no significant difference of c.677C>T genotypes between cases and controls was found, a clear increase of c.1298CC genotype was observed among RA patients (OR=2.59; p=0.0093). Our results suggest that MTHFR c.1298CC genotype may be considered a low-penetrance susceptibility factor for RA and point out a possible role of folate metabolism in the etiology of the disease.
The c.1298A>C polymorphism in the Methylenetetrahydrofolate Reductase (MTHFR) gene is risk factor for Rheumatoid Arthritis
RUBINI, Michele;PADOVAN, Melissa;BOSI, Simona;BARICORDI, Olavio;CARTURAN, Sabrina;CAVALLARO, Alessandra;FOTINIDI, Maria;MASSARA, Alfonso;GOVONI, Marcello;TROTTA, Francesco
2006
Abstract
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation that causes joint deformity, pain, functional limitations and psychological distress leading to work disability and consequent relevant social and individual costs. RA is a complex disease that results from the interplay between genetic and environmental factors. Identification of the genetic factors involved in the pathogenesis of RA could be crucial for early diagnosis and development of treatment strategies directed at the cause of the disease. However, still little is known susceptibility genes for RA. Although HLA-DRB1 is the main RA gene, it accounts for only part of the genetic risk for RA. Association studies suggested that other genes, including TNFR2, PADI4, SLC22A4, RUNX1, and PTPN22 play a role in the etiology of the disease. Metotrexate (MTX) is the first line treatment for RA and its efficacy has been reported to be dependent on gene variant in the Methylenetetrahydrofolate Reductase (MTHFR) gene. To assess the possible role of MTHFR polymorphisms in the etiology of RA, we genotyped the c.677C>T and the c.1298A>C variant in MTHFR gene in a group of 217 Italian RA patients and in a matched group of healthy controls. While no significant difference of c.677C>T genotypes between cases and controls was found, a clear increase of c.1298CC genotype was observed among RA patients (OR=2.59; p=0.0093). Our results suggest that MTHFR c.1298CC genotype may be considered a low-penetrance susceptibility factor for RA and point out a possible role of folate metabolism in the etiology of the disease.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
