title: The IkappaBL gene polymorphism influences risk of acquiring systemic lupus erythematosus and Sjögren's syndrome.
abstract: The human inhibitory kappaB-like gene (IkappaBL) maps to a chromosomal region approximately 25 kb telomeric of the TNF gene at 6p21.3. IkappaBL encodes a protein related to IkappaBalpha that may interact with members of the NF-kappaB/Rel family. We evaluated the role of IkappaBL gene polymorphism in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). Genomic DNA isolated from individuals with SLE (n = 134), pSS (n = 67) and from individuals matched for age, sex, and ethnicity (n = 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 IkappaBL 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 IKBL-62T+738T/TNF-308G-238G (TTGG) and TTAG because of linkage disequilibrium between IKBL-62T and TNF-308A. Our findings indicate that the IkappaBL gene influences the risk of developing SLE and pSS.
authors.affiliation: Cellular Biology and Immunogenetics Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia.
authors.forename: John
authors.initials: J
authors.lastname: Castiblanco
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012859:Sjogren's Syndrome / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000949:Histocompatibility Antigens Class II; C120111:NFKBIL1 protein, human; D014409:Tumor Necrosis Factor-alpha