Abstract
An association study and a linkage analysis were carried out in parallel in order to investigate the association of the inducible nitric oxide synthase (NOS2) gene promoter polymorphism with rheumatoid arthritis (RA) predisposition and/or outcome including a −954G-C mutation, a di-allelic (TAAA)n marker and the highly polymorphic (CCTTT). The −954G-C point mutation occurred non-polymorphic and the di-allelic (TAAA)n marker was not associated with RA predisposition. The (CCTTT)nlocus showed a trend for RA association in the case-control study, however, stratification data by Class II status did not yield significant effect and overall, the family study showed no significant association nor linkage for any of the markers under study using TDT and non-parametric linkage respectively. Finally, no influence was detected regarding any of the clinical parameters tested. After evaluating for the first time the influence of NOS2 promoter polymorphism in RA, it seems to have no major effect on disease susceptibility and/or outcome.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Weinberg JB . Nitric oxide production and nitric oxide synthase type 2 expression by human mononuclear phagocytes: a review Mol Med 1998 4: 557–591
Stefanovic-Racic M, Stadler J, Evans CH . Nitric oxide and arthritis Arthritis Rheum 1993 36: 1036–1044
Clancy RM, Amin AR, Abramson SB . The role of nitric oxide in inflammation and immunity Arthritis Rheum 1998 41: 1141–1151
St Clair EW, Wilkinson WE, Lang T et al. Increased expression of blood mononuclear cell nitric oxide synthase type 2 in rheumatoid arthritis J Exp Med 1996 184: 1173–1178
van’t Hof RJ, Hocking L, Wright PK, Ralston SH . Nitric oxide is a mediator of apoptosis in the rheumatoid joint Rheumatology 2000 39: 1004–1008
Kolb H, Kolb-Bachofen V . Nitric oxide in autoimmune disease: cytotoxic or regulatory mediator? Immunol Today 1998 19: 556–561
Kun JF, Mordmuller B, Lell B, Lehman LG, Luckner D, Kremsner PG . Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria Lancet 1998 351: 265–266
Bellamy R, Hill AV . A bi-allelic tetranucleotide repeat in the promoter of the human inducible nitric-oxide synthase gene Clin Genet 1997 52: 192–193
Xu W, Liu L, Emson PC, Harrington CR, Charles IG . Evolution of a homopurine-homopyrimidine pentanucleotide repeat sequence upstream of the human inducible nitric oxide synthase gene Gene 1997 204: 165–170
Warpeha KM, Xu W, Liu L et al. Genotyping and functional analysis of a polymorphic (CCTTT)n repeat of NOS2A in diabetic retinopathy FASEB 1999 13: 1825–1832
Pascual M, Nieto A, Lopez-Nevot MA et al. Rheumatoid arthritis in southern Spain: towards a unifying role of the class II region in disease predisposition Arthritis Rheum 2001 44: 307–314
Martin J, Calzada JE, Nieto A . Inducible nitric oxide synthase (NOS2) gene polymorphism and parasitic disease Lancet 1999 353: 72
Johannesen J, Pociot F, Kristiansen OP, Karlsen AE, Nerup J . DIEGG and DSGD. No evidence for linkage in the promoter region of the inducible nitric oxide synthase gene (NOS2) in a Danish type 1 diabetes population Genes Immun 2000 1: 362–366
Glenn CL, Wang WY, Morris BJ . Different frequencies of inducible nitric oxide synthase genotypes in older hypertensives Hypertension 1999 33: 927–932
Xu W, Humphries S, Tomita M et al. Survey of the allelic frequency of a NOS2A promoter microsatellite in human populations: assessment of the NOS2A gene and predisposition to infectious disease Nitric Oxide 2000 4: 379–383
Martinez A, Fernandez-Arquero M, Pascual-Salcedo D et al. Primary association of tumor necrosis factor-region genetic markers with susceptibility to rheumatoid arthritis Arthritis Rheum 2000 43: 1366–1370
Johannesen J, Tarnow L, Parving HH, Nerup J, Pociot F . CCTTT-repeat polymorphism in the human NOS2-promoter confers low risk of diabetic nephropathy in type 1 diabetic patients Diabetes Care 2000 23: 560–562
Wei XQ, Charles IG, Smith A et al. Altered immune responses in mice lacking inducible nitric oxide synthase Nature 1995 375: 408–411
Konno S, Hizawa N, Yamaguchi E, Jinushi E, Nishimura M . (CCTTT)n repeat polymorphism in the NOS2 gene promoter is associated with atopy J Allergy Clin Immunol 2001 108: 810–814
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by grant SAF00-213 from Plan Nacional de I+D (CICYT).
Rights and permissions
About this article
Cite this article
Pascual, M., López-Nevot, M., Cáliz, R. et al. Genetic determinants of rheumatoid arthritis: the inducible nitric oxide synthase (NOS2) gene promoter polymorphism. Genes Immun 3, 299–301 (2002). https://doi.org/10.1038/sj.gene.6363856
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363856
Keywords
This article is cited by
-
Osteoprotegerin and MTHFR gene variations in rheumatoid arthritis: association with disease susceptibility and markers of subclinical atherosclerosis
Scientific Reports (2022)
-
IL-1 β gene (+3954 C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms associate with early aseptic loosening of arthroplasties
Scientific Reports (2022)