Two independent functional risk haplotypes in TNIP1 are associated with systemic lupus erythematosus
Arthritis & Rheumatism, 07/27/2012
Adrianto I et al. – The results confirmed the association signals between Systemic lupus erythematosus (SLE) and TNIP1 variants in multiple populations and provide new insight into the mechanism by which TNIP1 variants may contribute to SLE pathogenesis.Methods
- The authors fine–mapped TNIP1, TNIP2, and TAX1BP1 in a total of 8372 SLE cases and 7492 healthy controls from European–ancestry, African–American, Hispanic, East Asian, and African–American Gullah populations.
- Levels of TNIP1 mRNA and ABIN1 protein were analyzed using quantitative RT–PCR and Western blotting, respectively, in EBV–transformed human B cell lines.
- They found significant associations between genetic variants within TNIP1 and SLE but not in TNIP2 or TAX1BP1.
- After resequencing and imputation, they identified two independent risk haplotypes within TNIP1 in individuals of European–ancestry that were also present in African–American and Hispanic populations.
- These risk haplotypes produced lower levels of TNIP1 mRNA and ABIN1 protein suggesting they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression.