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Title: Linkage disequilibrium analysis of chromosome 12q14-15 in multiple sclerosis: delineation of a 118-kb interval around interferon-gamma (IFNG) that is involved in male versus female differential susceptibility
Authors: Goris, An ×
Heggarty, S
Marrosu, M G
Graham, C
Billiau, Alfons
Vandenbroeck, K #
Issue Date: Dec-2002
Series Title: Genes and immunity vol:3 issue:8 pages:470-6
Abstract: We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population. This association could refer to a functional polymorphism within IFNG or could be due to linkage disequilibrium between the IFNG marker and a neighbouring susceptibility locus. Within the average reach of linkage disequilibrium, various other candidate genes are located. Among these the most striking ones are the genes coding for the cytokines interleukin-22 (IL-22) and interleukin-26 (IL-26) that constitute together with IFNG a cytokine cluster on chromosome 12q14. To determine more precisely the location of this gender-associated susceptibility locus, we have now performed a more extensive linkage disequilibrium screen of this region using nine additional microsatellite markers. This locus appeared to be confined to a 118-kb interval that is bordered by the markers D12S313 and D12S2511, in which IFNG itself remains the main candidate gene. Haplotype analysis confirmed that this MS-associated locus protects males from developing MS according to a recessive or allele-dosage model. Our results indicate that the well-documented gender differences in susceptibility to MS are at least partially caused by genetic factors in the region surrounding IFNG.
URI: 
ISSN: 1466-4879
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Laboratory of Immunobiology (Rega Institute)
Laboratory for Neuroimmunology
× corresponding author
# (joint) last author

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