A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid arthritis.
BACKGROUND
We determined the contribution of the methylene tetrahydrofolate reductase (MTHFR) 677 C>T and 1298 A>C gene polymorphisms to the susceptibility to rheumatoid arthritis (RA). We also assessed whether these two MTHFR gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction, in a series of Spanish patients with RA.


METHODS
Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo and Hospital San Carlos, Madrid, were studied. Patients and controls (n = 865) were genotyped using predesigned TaqMan SNP genotyping assays.


RESULTS
No significant differences in allele or genotype frequencies for the MTHFR gene polymorphisms between RA patients and controls were found. Also, no association between the MTHFR 677 C>T polymorphism and CV events or endothelial dysfunction was observed. However, the MTHFR 1298 allele C frequency was increased in patients with CV events after 5 years (38.7% versus 30.3%; odds ratio = 1.45; 95% confidence interval = 1.00 to 2.10; P = 0.04) and 10 years (42.2% versus 31.0%; odds ratio = 1.62; 95% confidence interval = 1.08 to 2.43; P = 0.01) follow up. Moreover, patients carrying the MTHFR 1298 AC and CC genotypes had a significantly decreased flow-mediated endothelium-dependent vasodilatation (4.3 +/- 3.9%) compared with those carrying the MTHFR 1298 AA genotype (6.5 +/- 4.4%) (P = 0.005).


CONCLUSIONS
Our results show that the MTHFR 1298 A>C gene polymorphism confers an increased risk for subclinical atherosclerosis and CV events in patients with RA.
Palomino-Morales
Rogelio
R
Instituto de Parasitología y Biomedicina Lopez-Neyra, CSIC, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento s/n Armilla, Granada 18100, Spain.
Gonzalez-Juanatey
Carlos
C
Vazquez-Rodriguez
Tomas R
TR
Rodriguez
Luis
L
Miranda-Filloy
Jose A
JA
Fernandez-Gutierrez
Benjamin
B
Llorca
Javier
J
Martin
Javier
J
Gonzalez-Gay
Miguel A
MA
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D050197:Atherosclerosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013030:Spain / Q000453:epidemiology
D042965:Methylenetetrahydrofolate Reductase (NADPH2)