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An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians.

Abstract

BACKGROUND

Multiple 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.

METHODS

We 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.

RESULTS

Marginally 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.

CONCLUSION

Our 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.

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  • Authors+Show Affiliations

    ,

    The Institute for Immunology and Allergy Research, Westmead Millennium Institute, Westmead Campus, University of Sydney, Westmead, NSW 2145, Australia. mbugeja@med.usyd.edu.au

    , , , ,

    Source

    BMC medical genetics 7: 2006 Jul 26 pg 64

    MeSH

    Australia
    Chemokine CCL11
    Chemokine CCL2
    Chemokines, CC
    Chromosomes, Human, Pair 17
    Female
    Genetic Predisposition to Disease
    Genotype
    Haplotypes
    Humans
    Linkage Disequilibrium
    Male
    Multigene Family
    Multiple Sclerosis
    Polymorphism, Single Nucleotide
    Sequence Analysis, DNA

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16872505

    Citation

    Bugeja, Matthew J., et al. "An Investigation of Polymorphisms in the 17q11.2-12 CC Chemokine Gene Cluster for Association With Multiple Sclerosis in Australians." BMC Medical Genetics, vol. 7, 2006, p. 64.
    Bugeja MJ, Booth D, Bennetts B, et al. An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians. BMC Med Genet. 2006;7:64.
    Bugeja, M. J., Booth, D., Bennetts, B., Heard, R., Rubio, J., & Stewart, G. (2006). An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians. BMC Medical Genetics, 7, p. 64.
    Bugeja MJ, et al. An Investigation of Polymorphisms in the 17q11.2-12 CC Chemokine Gene Cluster for Association With Multiple Sclerosis in Australians. BMC Med Genet. 2006 Jul 26;7:64. PubMed PMID: 16872505.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians. AU - Bugeja,Matthew J, AU - Booth,David, AU - Bennetts,Bruce, AU - Heard,Robert, AU - Rubio,Justin, AU - Stewart,Graeme, Y1 - 2006/07/26/ PY - 2006/05/22/received PY - 2006/07/26/accepted PY - 2006/7/29/pubmed PY - 2006/8/30/medline PY - 2006/7/29/entrez SP - 64 EP - 64 JF - BMC medical genetics JO - BMC Med. Genet. VL - 7 N2 - BACKGROUND: Multiple 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. METHODS: We 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. RESULTS: Marginally 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. CONCLUSION: Our 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. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/16872505/An_investigation_of_polymorphisms_in_the_17q11_2_12_CC_chemokine_gene_cluster_for_association_with_multiple_sclerosis_in_Australians_ L2 - https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-7-64 DB - PRIME DP - Unbound Medicine ER -