RGD Reference Report - Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes. - Rat Genome Database

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Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes.

Authors: Zhernakova, A  Alizadeh, BZ  Eerligh, P  Hanifi-Moghaddam, P  Schloot, NC  Diosdado, B  Wijmenga, C  Roep, BO  Koeleman, BP 
Citation: Zhernakova A, etal., Genes Immun. 2006 Oct;7(7):544-9. Epub 2006 Jul 20.
RGD ID: 2307102
Pubmed: PMID:16855620   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.gene.6364326   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCL5Humantype 1 diabetes mellitus susceptibilityIAGP DNA:SNPs:rs4251719 more ...RGD 
Ccl5Rattype 1 diabetes mellitus susceptibilityISOCCL5 (Homo sapiens)DNA:SNPs:rs4251719 more ...RGD 
Ccl5Mousetype 1 diabetes mellitus susceptibilityISOCCL5 (Homo sapiens)DNA:SNPs:rs4251719 more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl5  (C-C motif chemokine ligand 5)

Genes (Mus musculus)
Ccl5  (C-C motif chemokine ligand 5)

Genes (Homo sapiens)
CCL5  (C-C motif chemokine ligand 5)


Additional Information