Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study

Abstract

BackgroundVarious cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA.MethodsPolymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed.ResultsThe IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity.ConclusionsWe here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA.

Association of Tumor Necrosis Factor-Alpha -308 G>A Polymorphism With Rheumatoid Arthritis in Two North Indian Cohorts

“…Some studies have reported a positive association of TNF-α -308 alleles with RA 3,16,31-34 while others have reported lack of association with RA. 36,[48][49][50][51][52] In conformity with the majority of previous studies, the present study failed to demonstrate any association between the TNF-α -308 G>A promoter polymorphism and RA in cohort 1. Interestingly, the comparison between RA patients who were RF positive and RF negative revealed a marginally significant difference in the allele frequencies (p=0.05, OR=2.86, 0.96-8.52 at 95% CI).…”

“…The frequency in the control population of Punjab (cohort 1) was 8.3%, which was similar to Chinese (7.7%) 3 and Czech (9.7%), 10 and higher than Japanese (3.3%), Egyptian (3.1%) populations, and the North Indian (4.9%) population from Uttar Pradesh. [32][33][34] The frequency in cohort 2 comprising the Jammu and Kashmir population (25%) was nearly similar to that reported in European populations including North Swedish (24%), 19 Dutch (23.8%), 35 and Netherlands (19%) 36 but lower than Saudi Arabian (31.0%) 28 population. The frequency of A allele in Jammu and Kashmir was higher compared to the population of Punjab.…”

“…This finding was in line with other studies from populations of France, America, Taiwan and Netherlands which have also reported higher percentage of female RA patients (78%, 75.7%, 75.4%, and 73.5%, respectively). 36,[38][39][40] The results implied that sex may have a significant effect on susceptibility to RA, with the disease being three times more frequent in females than in males. Moreover, it has been reported that hypoandrogenicity is responsible for RA in younger women.…”

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

“…Clinical characteristics such as age at onset, RF positivity, joint erosion and extra-articular manifestations were compared among patients, and it was found that patients with IL-8 3'-UTR 2767AA genotype had a significantly younger age of onset of RA than patients without that genotype [118] . In caucasian RA patients and healthy controls the 781 C/T (2227306) SNP of IL-8 gene was examined with the result that CC genotype is associated with the early onset of RA [137] .…”

A comprehensive meta-analysis of the association between three <i>IL</i>1B polymorphisms and rheumatoid arthritis

“…IL1B is 7020 bp in length and contains 826 polymorphisms according to the NCBI dbSNP database. Among them, IL1B-31 [10][11][12][13][14], IL1B-511 [9][10][11][14][15][16][17][18][19][20][21][22][23][24][25][26] and IL1B + 3954 [9][10][11]14,[16][17][18][19][20][21][22][23][25][26][27][28][29] are the most studied in the association with RA.…”