Abstract
BackgroundMultiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterised by inflammation and neuronal degeneration. It is believed to result from the complex interaction of a number of genes, each with modest effect. Chemokines are vital to the migration of cells to sites of inflammation, including the CNS, and many are implicated in MS pathogenesis. Most of the CC chemokine genes are encoded in a cluster on chromosome 17q11.2-12, which has been identified in a number of genome wide screens as being potentially associated with MS.MethodsWe conducted a two-stage analysis to investigate the chemokine gene cluster for association with MS. After sequencing the chemokine genes in several DNA pools to identify common polymorphisms, 12 candidate single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of Australian MS trio families.ResultsMarginally significant (uncorrected) transmission distortion was identified for four of the SNPs after stratification for several factors. We also identified marginally significant (uncorrected) transmission distortion for haplotypes encompassing the CCL2 and CCL11 genes, using two independent cohorts, which was consistent with recent reports from another group.ConclusionOur results implicate several chemokines as possibly being associated with MS susceptibility, and given that chemokines and their receptors are suitable targets for therapeutic agents, further investigation is warranted in this region.
Highlights
Multiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterised by inflammation and neuronal degeneration
Identification and analysis of single-nucleotide polymorphisms (SNPs) in CC chemokine genes by DNA pool sequencing The CC chemokine genes were scanned using DNA pool sequencing in order to identify common polymorphisms in the region, including the potential identification of novel SNPs, and to establish whether associations might exist for these SNPs
50 SNPs were identified across the CC chemokine gene cluster, 48 of which were known; novel SNPs were detected in CCL8 and CCL15
Summary
Multiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterised by inflammation and neuronal degeneration. Chemokines are vital to the migration of cells to sites of inflammation, including the CNS, and many are implicated in MS pathogenesis. Most of the CC chemokine genes are encoded in a cluster on chromosome 17q11.2-12, which has been identified in a number of genome wide screens as being potentially associated with MS. Multiple sclerosis (MS) is the most common chronic neurological disease in young adults It is characterised by inflammation of the central nervous system (CNS), believed to be the result of an autoimmune reaction resulting in demyelination and destruction of neural supporting cells [1]. Multiple regions of potential linkage and association with MS have been identified, suggesting that genetic predisposition to MS might result from the modest contribution of many genetic factors, which, if identified, may present important new therapeutic targets [4]. Two smaller subgroups have been identified; the CX3C chemokines, and the C chemokines
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