We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes.
- Authors
Zhernakova, A.; Alizadeh, B. Z.; Eerligh, P.; Hanifi-Moghaddam, P.; Schloot, N. C.; Diosdado, B.; Wijmenga, C.; Roep, B. O.; Koeleman, B. P. C.
- Abstract
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.Genes and Immunity (2006) 7, 544–549. doi:10.1038/sj.gene.6364326; published online 20 July 2006
- Subjects
GENETICS of diabetes; T cells; CHEMOKINES; AUTOIMMUNE diseases; GENETIC polymorphisms; CELL proliferation; CHROMOSOMES; MEDICAL genetics
- Publication
Genes & Immunity, 2006, Vol 7, Issue 7, p544
- ISSN
1466-4879
- Publication type
Article
- DOI
10.1038/sj.gene.6364326