A possible role of c.1298A>C polymorphism in the MTHFR (Methylene Tetrahydrofolate Reductase) gene in the aetiology of RA has been suggested by the finding of a two-fold excess of 1298CC homozygotes in a case-control study in a Jewish population (1), but has not been confirmed in American cases with Caucasian or African origin (2). In order to assess the association between common polymorphisms in the MTHFR gene and the risk of RA we set up a case-control study using a genetically homogenous cohort of 217 consecutive Caucasian patients from North Italy and a group of 251 healthy subjects, matched for age, gender, ethnicity and geographical origin. All patients fulfilled the revised criteria of the American College of Rheumatology for the diagnosis of RA. All subjects included in this study were genotyped for MTHFR c.677C>T (rs1801133) and c.1298A>C (rs1801131) polymorphisms by polymerase chain reaction (PCR) followed by digestion with restriction enzymes, electrophoresis on polyacrylamide gel (5%), and silver staining. As reported in Table 1, in RA patients c.677C>T genotype frequencies were not significantly different from controls, although a decrease of 677CT heterozygotes was observed. A clear excess of 1298CC homozygotes among patients (12.0%) compared to controls (4.8%) was seen in c.1298A>C polymorphism (p=0.009). This genotype resulted associated with a significant OR value of 2.62 (95% C.I. 1.26-5.45). Comparing 1298CC homozygotes with subjects carrying other genotypes (pooling 1298AA and 1298AC genotypes), the calculated OR was 2.71 (95% C.I. 1.33-5.51; p=0.006). Our result is in agreement with that reported in a case-control study in a Jewish population (1), and indicates that subjects carrying the 1298CC genotype, that in North Italy are around 5% of population (3), are at increased risk of developing RA. We hypothesize that the lack of association reported in the American populations could be related to the high level of blood folate in the United States populations due to fortification of flour products with folic acid since 1998.

The c.1298A>C polymorphism in the methylenetetrahydrofolate reductase gene is associated with rheumatoid arthritis susceptibility in Italian patients

RUBINI, Michele;PADOVAN, Melissa;BARICORDI, Olavio;FOTINIDI, Maria;GOVONI, Marcello;TROTTA, Francesco
2008

Abstract

A possible role of c.1298A>C polymorphism in the MTHFR (Methylene Tetrahydrofolate Reductase) gene in the aetiology of RA has been suggested by the finding of a two-fold excess of 1298CC homozygotes in a case-control study in a Jewish population (1), but has not been confirmed in American cases with Caucasian or African origin (2). In order to assess the association between common polymorphisms in the MTHFR gene and the risk of RA we set up a case-control study using a genetically homogenous cohort of 217 consecutive Caucasian patients from North Italy and a group of 251 healthy subjects, matched for age, gender, ethnicity and geographical origin. All patients fulfilled the revised criteria of the American College of Rheumatology for the diagnosis of RA. All subjects included in this study were genotyped for MTHFR c.677C>T (rs1801133) and c.1298A>C (rs1801131) polymorphisms by polymerase chain reaction (PCR) followed by digestion with restriction enzymes, electrophoresis on polyacrylamide gel (5%), and silver staining. As reported in Table 1, in RA patients c.677C>T genotype frequencies were not significantly different from controls, although a decrease of 677CT heterozygotes was observed. A clear excess of 1298CC homozygotes among patients (12.0%) compared to controls (4.8%) was seen in c.1298A>C polymorphism (p=0.009). This genotype resulted associated with a significant OR value of 2.62 (95% C.I. 1.26-5.45). Comparing 1298CC homozygotes with subjects carrying other genotypes (pooling 1298AA and 1298AC genotypes), the calculated OR was 2.71 (95% C.I. 1.33-5.51; p=0.006). Our result is in agreement with that reported in a case-control study in a Jewish population (1), and indicates that subjects carrying the 1298CC genotype, that in North Italy are around 5% of population (3), are at increased risk of developing RA. We hypothesize that the lack of association reported in the American populations could be related to the high level of blood folate in the United States populations due to fortification of flour products with folic acid since 1998.
2008
Rubini, Michele; Padovan, Melissa; Baricordi, Olavio; Fotinidi, Maria; Govoni, Marcello; Trotta, Francesco
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/521445
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