Inducible but not endothelial nitric oxide synthase polymorphism is associated with susceptibility to rheumatoid arthritis in northwest Spain.
OBJECTIVE
To assess the influence of inducible and endothelial nitric oxide synthase (iNOS and eNOS) polymorphisms in susceptibility to rheumatoid arthritis (RA).


METHODS
Two hundred RA patients fulfilling the 1987 American College of Rheumatology classification criteria followed at the out-patient rheumatology clinic of the Hospital Xeral-Calde (Lugo, Spain) and 251 ethnically matched controls were studied. Patients and controls were genotyped by PCR-based techniques for a multiallelic (CCTTT)(n) repeat in the promoter region of the iNOS gene and for a T/C polymorphism at position -786 in the promoter region and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene.


RESULTS
No significant difference in allele or genotype frequencies for either polymorphism in the eNOS gene was observed between RA patients and controls. The overall iNOS CCTTT(n) allelic or genotypic distribution did not show statistical significant differences between RA patients and controls. Interestingly, when we stratified the iNOS alleles into short (8-11) and long (12-16) repeats, significant differences were observed between RA patients and controls (P = 0.021; odds ratio = 1.37, 95% confidence interval 1.04-1.81). Of note, individuals carrying two alleles with a repeat number less than 12 (fewer than 196 base pairs) exhibited a double risk of developing RA (P = 0.005, odds ratio 2.26, 95% confidence interval 1.25-4.08).


CONCLUSIONS
Significant differences in the iNOS promoter polymorphism genotype frequency between northwest Spanish RA patients and controls suggest a potential role for this polymorphism in susceptibility to RA.
Gonzalez-Gay
M A
MA
Division of Rheumatology, Hospital Xeral-Calde, c/ Dr Ochoa s/n, 27004, Lugo, Spain. miguelaggay@hotmail.com
Llorca
J
J
Sanchez
E
E
Lopez-Nevot
M A
MA
Amoli
M M
MM
Garcia-Porrua
C
C
Ollier
W E R
WE
Martin
J
J
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012217:Rheumatoid Factor / Q000235:genetics
D012217:Rheumatoid Factor; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III