Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetesZhernakova, A., Alizadeh, B. Z., Eerligh, P., Hanifi-Moghaddam, P., Schloot, N. C., Diosdado, B., Wijmenga, C., Roep, B. O. & Koeleman, B. P. C., 1-Mar-2006, In : GENES AND IMMUNITY. 7, 7, p. 544-549 6 p.
Research output: Contribution to journal › Article › Academic › peer-review
RANTES ( regulated on activation, normal T-cell expressed and secreted) is a T-helper type 1 (Th1) chemokine that promotes T-cell activation and proliferation. RANTES is genetically associated with asthma, sarcoidosis and multiple sclerosis. The concentration of RANTES is increased at inflammation sites in different autoimmune diseases. Type 1 diabetes (T1D) is a Th1-mediated disease with complex genetic predisposition. We tested RANTES as a candidate gene for association with T1D using three single-nucleotide polymorphism ( SNP) variants (rs4251719, rs2306630 and rs2107538) to capture haplotype information. The minor alleles of all SNPs were transmitted less frequently to T1D offspring (transmission rates 37.3% (P = 0.002), 38.7% (P = 0.007) and 41.0% ( P = 0.01)) and were less frequently present in patients compared to controls (P = 0.009, 0.03 and 0.04, respectively). A similar protective effect was observed for the haplotype carrying three minor alleles (transmission disequilibrium test (TDT): P = 0.003; odds ratio (OR) = 0.55; confidence interval (CI): 0.37 - 0.83; case/control: P 0.03; OR 0.74; CI: 0.55 - 0.98). Both patients and controls carrying the protective haplotype express significantly lower serum levels of RANTES compared to non-carriers. Subsequently, we tested a cohort of 310 celiac disease patients, but failed to detect association. RANTES SNPs are significantly associated with RANTES serum concentration and development of T1D. The rs4251719* A-rs2306630* A-rs2107538* A haplotype associated with low RANTES production confers protection from T1D. Our data imply that RANTES is associated with T1D both genetically and functionally, and contributes to diabetes-prone Th1 cytokine profile.
|Number of pages||6|
|Journal||GENES AND IMMUNITY|
|Publication status||Published - 1-Mar-2006|
- RANTES, CCL5, autoimmune diseases, type 1 diabetes, celiac disease, Th1 cytokine profile, RHEUMATOID-ARTHRITIS, T-CELLS, CHEMOKINE RECEPTORS, SIGNALING PATHWAYS, IMMUNE-RESPONSE, POLYMORPHISM, PROMOTER, DISEASE, MICE, ACTIVATION