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

The Institute for Immunology and Allergy Research, Westmead Millennium Institute, Westmead Campus, University of Sydney, Westmead, NSW 2145, Australia

D R Booth

The Institute for Immunology and Allergy Research, Westmead Millennium Institute, Westmead Campus, University of Sydney, Westmead, NSW 2145, Australia

B H Bennetts

Department of Molecular Genetics, The Children’s Hospital at Westmead, University of Sydney, Westmead, NSW 2145, Australia, Discipline of Paediatrics and Child Health, University of Sydney, NSW 2006, Australia

R NS Heard

The Institute for Immunology and Allergy Research, Westmead Millennium Institute, Westmead Campus, University of Sydney, Westmead, NSW 2145, Australia

G J Stewart

The Institute for Immunology and Allergy Research, Westmead Millennium Institute, Westmead Campus, University of Sydney, Westmead, NSW 2145, Australia, stewartg{at}westgate.wh.usyd.edu.au

Susceptibility to multiple sclerosis (MS) is believed to result from the complex interaction of a number of genes, each with modest effect. Vital to the migration of cells to sites of inflammation, including the central nervous system, are chemokines, many of which are implicated in MS pathogenesis. Most of the CXC chemokine genes are encoded in a cluster on chromosome 4q13.3-21.1, which has been identified in several genome-wide screens as being potentially associated with MS. We conducted a two-stage analysis to investigate the chemokine gene cluster for association with MS. Initially, we sequenced the chemokine genes in several DNA pools to identify common polymorphisms, and then genotyped selected SNPs in 373 Australian MS trio families. We found no evidence that the CXC chemokine gene cluster is genetically associated with MS. However, the existence of common variants conferring small risk factors or rare variants with significant risk cannot be excluded.

Key Words: autoimmune disease • Caucasians • CXC chemokines • DNA pool sequencing • genetics • multiple sclerosis

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