Abstract
Evidence suggests that interleukin-1 receptor-associated kinase-1 (IRAK1), fundamental in the toll-like receptor pathway (TLR), may play a more specific role in atherosclerosis. METHODS: Caucasian women (N=529) and men (N=467) from the Diabetes Heart Study (DHS) were genotyped at four loci within the IRAK1 gene located on the X chromosome. Generalized estimating equations (GEE1) were used to evaluate association with C-reactive protein (CRP) for both single SNP and haplotype analyses. RESULTS: For each SNP genotyped, Caucasian women carrying one or two copies of the variant allele had greater CRP concentrations than those carrying the common genotype in both crude and adjusted models. There were 2 major haplotypes, CTTT (82%) and its complement TCCG (13%). The presence of the TCCG haplotype was associated with greater CRP concentrations in Caucasian women (p=0.0004) and this relationship was maintained after adjustment for age, BMI, smoking, diabetes, and cholesterol-lowering therapy (p=0.003). There was no association between CRP and IRAK1 SNPs in Caucasian men. CONCLUSION: Variation in the IRAK1 gene is associated with CRP concentration in Caucasian women in DHS. Further studies are needed to reproduce the current finding and to understand the biological relationship between IRAK1 and inflammation related to atherosclerosis.