Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population.
Rheumatoid arthritis is a chronic autoimmune disorder associated with altered expression of pro- and anti-inflammatory cytokines in the affected tissues. The aim of this study was to investigate the association between promoter polymorphisms of TNFalpha and IL-10 gene with susceptibility, age of disease onset and disease severity in North Indian patients with rheumatoid arthritis (RA). SNPs at position -308 and -863 of TNF gene and -819/-592 and -1082 position of IL-10 gene were determined in 222 patients and 208 healthy controls using RFLP or ARMS method. Polymorphism TNF -308A was less prevalent among the patients (1.7%) than controls (4.9%; p = 0.01, OR: 0.32, 95% CI: 0.13-0.76). Among female patients, IL-10 -592A allele associated with higher baseline disease activity scores (5.77 +/- 1.99) than -592C (5.57 +/- 1.19; p = 0.04). Female patients carrying allele A of TNFalpha -863 had earlier age of onset of RA (33.99 +/- 9.6 years) than those with allele C (36.15 +/- 11.21 years; p = 0.043). In conclusion, allele A at TNFalpha -308 locus provides protection against RA in North Indian population while another TNF allele A at -863 position had weak association with earlier onset of disease in female patients. On the other hand promoter polymorphisms of IL-10 did not affect susceptibility but polymorphism at -819/-592A was associated with higher disease activity scores at baseline.
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. deepali64@yahoo.com
Deepali
D
Gambhir
Able
A
Lawrence
Amita
A
Aggarwal
Ramnath
R
Misra
Sudhir Kumar
SK
Mandal
Sita
S
Naik
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10