NO role of NOS2A susceptibility polymorphisms in rheumatoid arthritis.
Nitric oxide has been described as a trigger for the synthesis of proinflammatory mediators and as a cytotoxic molecule with a pivotal role in apoptosis at the joints of rheumatoid arthritis (RA) patients. Polymorphisms in the NOS2A gene, which codes for the inducible nitric oxide synthase [(i)NOS], have been tested for association with several autoimmune diseases such as Crohn's disease or type 1 diabetes. Moreover, the existence of correlated levels of (i)NOS protein and synovial cell apoptosis in RA patients, pointed to NOS2A as a good candidate gene involved in RA predisposition. The role of NOS2A was studied in 405 Spanish RA patients and in 398 ethnically matched healthy controls, through the analysis of five SNPs: two at the NOS2A promoter (rs2779251 and 2779248), other two exonic markers (Asp(346)Asp (rs1137933) and Ser(608)Leu (rs22518)) and the last one located at intron 7 (rs3729508). We also included other two widely-used promoter polymorphisms: the insertion/deletion (TAAA/-) and the (CCTTT)n microsatellite. No individual association of each single-marker or haplotype was found with RA susceptibility. Our data show the low linkage disequilibrium between these NOS2A SNPs and the alleles of the (CCTTT)n microsatellite, corroborating in a Spanish population the observation previously described in British and Gambian population. The present data do not support a causative role of NOS2A polymorphisms in RA predisposition.
Varadé
Jezabel
J
Immunology Department, Hospital Clínico San Carlos, Prof. Martin Lagos s/n, 28040 Madrid, Spain. gezabelvarade@gmail.com
Lamas
José Ramón
JR
Fernández-Arquero
Miguel
M
Jover
Juan Angel
JA
de la Concha
Emilio G
EG
Martínez
Alfonso
A
Fernández-Gutierrez
Benjamín
B
Urcelay
Elena
E
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011110:Polymorphism, Genetic; D013030:Spain
D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II