The I kappa BL gene polymorphism influences risk of acquiring systemic lupus erythematosus and Sjogren's syndrome

The human inhibitory kappa B-like gene (IKBL) maps to a chromosomal region similar to 25 kb telomeric of the TNF gene at 6p2l.3. I kappa BL encodes a protein related to I kappa B alpha that may interact with members of the NF-kappa B/Rel family. We evaluated the rote of I kappa BL gene polymorphism in systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (pSS). Genomic DNA isolated from individuals with SLE (n= 134), pSS (n = 67) and from individuals matched for age, sex, and ethnicity In = 423) was genotyped for Delta-473, -62T/A and +738T/C polymorphisms. The -62A allele was associated with a decrease in the risk of acquiring SLE in a recessive manner; whereas the +738C allele was associated with a more than twofold and threefold increase in the risk of SLE and pSS respectively, relative to the +738T allele. Four haplotypes were observed for the I kappa KBL polymorphisms. Haplotype -62A+738T (AT) was associated with a 37% decrease in the risk of SLE, whereas AC tended to increase the risk of developing pSS. Using previously reported TNF data, an almost twofold increased in the risk of SLE was observed between haplotypes I kappa BL-62T+738T/TNF-308G-238G (TTGG) and TTAG because of linkage disequilibrium between I kappa BL-62T and TNF-308A. Our findings indicate that the I kappa BL gene influences the risk of developing SLE and pSS. (c) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.