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

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.

• Publication year

  2006

• Venue

  BMC Medical Genetics

• Publication date

  2006-07-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1471-2350-7-64PMID 16872505PMCID 1550395
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• An investigation of polymorphisms in the 4q13.3-21.1 CXC chemokine gene cluster for association with multiple sclerosis in Australians

  2006cited by this paper
• Modulating CCR2 and CCL2 at the blood-brain barrier: relevance for multiple sclerosis pathogenesis.

  2006cited by this paper
• Association of haplotypes in the beta-chemokine locus with multiple sclerosis.

  2005cited by this paper
• Association of haplotypes in the β-chemokine locus with multiple sclerosis

  2005cited by this paper
• Haplotypes within genes of β-chemokines in 17q11 are associated with multiple sclerosis: a second phase study

  2005cited by this paper
• A high-density screen for linkage in multiple sclerosis.

  2005cited by this paper
• T cell costimulation by chemokine receptors

  2005cited by this paper
• Haploview: analysis and visualization of LD and haplotype maps

  2005cited by this paper
• An extended genome scan in 442 Canadian multiple sclerosis-affected sibships: a report from the Canadian Collaborative Study Group.

  2004cited by this paper
• CCL16/LEC powerfully triggers effector and antigen‐presenting functions of macrophages and enhances T cell cytotoxicity

  2004cited by this paper
• An Advanced Intercross Line Resolves Eae18 into Two Narrow Quantitative Trait Loci Syntenic to Multiple Sclerosis Candidate Loci1

  2004cited by this paper
• Evidence for a cluster of genes on chromosome 17q11–q21 controlling susceptibility to tuberculosis and leprosy in Brazilians

  2004cited by this paper
• Updated results of the United Kingdom linkage-based genome screen in multiple sclerosis.

  2003cited by this paper
• A mutated CCR5 gene may have favorable prognostic implications in MS

  2003cited by this paper
• A haplotype map of the human genome.

  2003cited by this paper
• A haplotype map of the human genome

  2003cited by this paper
• MCP-1-MCP-3–Eotaxin gene cluster influences HIV-1 transmission

  2003cited by this paper
• Identification of 11 novel and common single nucleotide polymorphisms in the interleukin-7 receptor-α gene and their associations with multiple sclerosis

  2003cited by this paper
• MCP-1 promoter polymorphism in Spanish patients with rheumatoid arthritis.

  2003cited by this paper
• A genome-wide screen for linkage disequilibrium in Australian HLA-DRB1*1501 positive multiple sclerosis patients.

  2003cited by this paper
• HaploBlockFinder: Haplotype Block Analyses

  2003influential reference
• The genetic analysis of multiple sclerosis in Europeans: concepts and design.

  2003cited by this paper
• Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q

  2003cited by this paper
• Expression of chemokines in the CSF and correlation with clinical disease activity in patients with multiple sclerosis

  2002cited by this paper
• Universal, robust, highly quantitative SNP allele frequency measurement in DNA pools

  2002cited by this paper
• Merlin—rapid analysis of dense genetic maps using sparse gene flow trees

  2002cited by this paper
• A whole genome screen for linkage disequilibrium in multiple sclerosis confirms disease associations with regions previously linked to susceptibility.

  2002cited by this paper
• Multiple sclerosis and optic neuritis: CCR5 and CXCR3 expressing T cells are augmented in blood and cerebrospinal fluid

  2002cited by this paper
• Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis

  2001cited by this paper
• Absence of Monocyte Chemoattractant Protein 1 in Mice Leads to Decreased Local Macrophage Recruitment and Antigen-Specific T Helper Cell Type 1 Immune Response in Experimental Autoimmune Encephalomyelitis

  2001influential reference
• Nomenclature for the description of human sequence variations

  2001cited by this paper
• A meta-analysis of genomic screens in multiple sclerosis

  2001cited by this paper
• A meta-analysis of genomic screens in multiple sclerosis. The Transatlantic Multiple Sclerosis Genetics Cooperative.

  2001cited by this paper
• Atopic Dermatitis Is Associated with a Functional Mutation in the Promoter of the C-C Chemokine RANTES1

  2000cited by this paper
• Increased numbers of CCR5+ interferon-gamma- and tumor necrosis factor-alpha-secreting T lymphocytes in multiple sclerosis patients.

  2000cited by this paper
• Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue.

  2000cited by this paper
• CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis

  2000cited by this paper
• TRANSFAC: an integrated system for gene expression regulation

  2000cited by this paper
• Increased numbers of CCR5+ interferon‐γ– and tumor necrosis factor‐α–secreting T lymphocytes in multiple sclerosis patients

  2000cited by this paper
• The −403 G→A promoter polymorphism in the RANTES gene is associated with atopy and asthma

  2000cited by this paper
• CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. Multiple Sclerosis Genetics Group.

  2000cited by this paper
• Induction of experimental autoimmune encephalomyelitis in C57BL / 6 mice deficient in either the chemokine macrophage inflammatory protein‐1α or its CCR5 receptor

  2000cited by this paper
• Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients.

  1999cited by this paper
• Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for eae7, a locus controlling susceptibility to monophasic remitting/nonrelapsing experimental allergic encephalomyelitis.

  1999cited by this paper
• Chemokines: extracellular messengers for all occasions?

  1999cited by this paper
• A generalization of the transmission/disequilibrium test for uncertain-haplotype transmission.

  1999influential reference
• Expression of MCP-1 by reactive astrocytes in demyelinating multiple sclerosis lesions.

  1999cited by this paper
• MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ hybridization study.

  1998cited by this paper
• Chemokines and leukocyte traffic

  1998cited by this paper
• Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions.

  1998cited by this paper
• Insights into the aetiology and pathogenesis of multiple sclerosis

  1998cited by this paper
• Differential CC chemokine-induced enhancement of T helper cell cytokine production.

  1997cited by this paper
• The CCR5 deletion mutation fails to protect against multiple sclerosis.

  1997cited by this paper
• Genetics of multiple sclerosis.

  1997cited by this paper
• Multiple sclerosis, multiple genes

  1997cited by this paper
• Genomewide scan of multiple sclerosis in Finnish multiplex families.

  1997cited by this paper
• Perivascular T Cells Express the Pro‐Inflammatory Chemokine RANTES mRNA in Multiple Sclerosis Lesions

  1997cited by this paper
• Identification of cell types producing RANTES, MIP-1 alpha and MIP-1 beta in rat experimental autoimmune encephalomyelitis by in situ hybridization.

  1997cited by this paper
• A YAC contig of the human CC chemokine genes clustered on chromosome 17q11.2.

  1996cited by this paper
• A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22

  1996cited by this paper
• Parametric and nonparametric linkage analysis: a unified multipoint approach.

  1996cited by this paper
• Chemokines and T lymphocyte activation: I. Beta chemokines costimulate human T lymphocyte activation in vitro.

  1996cited by this paper
• Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis.

  1995cited by this paper
• Monocyte chemotactic protein-1 (MCP-1), -2, and -3 are chemotactic for human T lymphocytes.

  1995cited by this paper
• An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis.

  1995cited by this paper
• Macrophage inflammatory protein-1 alpha in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological diseases.

  1995cited by this paper
• Monocyte chemotactic proteins MCP‐1, MCP‐2, and MCP‐3 are major attractants for human CD4+ and CD8+ T lymphocytes

  1994cited by this paper
• Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM).

  1993cited by this paper
• Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils

  1992cited by this paper
• Biology of the RANTES/SIS cytokine family.

  1991cited by this paper
• A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies.

  1991cited by this paper
• Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES

  1990cited by this paper
• A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes.

  1989cited by this paper
• New diagnostic criteria for multiple sclerosis: Guidelines for research protocols

  1983cited by this paper

• Immunologic analysis of CSF in patients with de novo diagnosed RRMS. The role of chemokines in the early phase of the disease.

  2024cites this paper
• Study on plasma CC chemokine ligand 2 level and its promoter region 2518A/G polymorphism in MS patients

  2020cites this paper
• Calculating the statistical significance of rare variants causal for Mendelian and complex disorders

  2017cites this paper
• Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis.

  2016cites this paper
• Association of monocyte chemoattractant protein-1 gene 2518A/G polymorphism with diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis.

  2016cites this paper
• Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

  2015cites this paper
• Expression of Ccl11 Associates with Immune Response Modulation and Protection against Neuroinflammation in Rats

  2012cites this paper
• Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (review).

  2011cites this paper
• Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis

  2010cites this paper
• Lack of Association between Promoter Gene Polymorphism (-318 C/T) and Multiple Sclerosis in Iranian Population

  2008cites this paper
• CCR5-Delta32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis.

  2007cites this paper
• Recent advances in genetic analysis of multiple sclerosis: genetic associations and therapeutic implications

  2007cites this paper
• CCR5-Δ32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis

  2007cites this paper
• A follow-up study of Nordic multiple sclerosis candidate gene regions

  2007cites this paper