Dataset Information

CCL genes in multiple sclerosis and systemic lupus erythematosus.

ABSTRACT: This follow up study aims to refine the roles of previously suggested candidate genes (CC chemokine ligands or CCLs) in multiple sclerosis (MS), and to test these markers in another autoimmune disorder, systemic lupus erythematosus (SLE). After stringent correction for multiple testing, we reject the importance of previously suggested borderline associations with CCLs in MS. A new finding is the differential distribution of CCL8 marker alleles and a haplotype in extreme severity subgroups of MS. In SLE, this study reveals strong associations with a marker and a haplotype encompassing the CCL14 gene, which suggests that a lupus relevant variant may lie within or in the proximity of this haplotype.

SUBMITTER: Vyshkina T

PROVIDER: S-EPMC5301077 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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CCL genes in multiple sclerosis and systemic lupus erythematosus.

Vyshkina Tamara T Sylvester Andrew A Sadiq Saud S Bonilla Eduardo E Perl Andras A Kalman Bernadette B

Journal of neuroimmunology 20080703 1-2

This follow up study aims to refine the roles of previously suggested candidate genes (CC chemokine ligands or CCLs) in multiple sclerosis (MS), and to test these markers in another autoimmune disorder, systemic lupus erythematosus (SLE). After stringent correction for multiple testing, we reject the importance of previously suggested borderline associations with CCLs in MS. A new finding is the differential distribution of CCL8 marker alleles and a haplotype in extreme severity subgroups of MS. ...[more]

PMID: 18602166

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Project description:Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P ?=?1.34×10(-8), OR ?=?1.22, CI 95% ?=?1.14-1.30; rs2004640: P ?=?4.60×10(-7), OR ?=?0.84, CI 95% ?=?0.78-0.90; rs10488631: P ?=?7.53×10(-20), OR ?=?1.63, CI 95% ?=?1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P ?=?0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P ?=?9.04×10(-22), OR ?=?1.75, CI 95% ?=?1.56-1.97) better explained the observed association (likelihood P-value ?=?1.48×10(-4)), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.

Dataset Information

CCL genes in multiple sclerosis and systemic lupus erythematosus.

Publications

CCL genes in multiple sclerosis and systemic lupus erythematosus.

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