title: Interleukin-6 gene promoter-572 C allele may play a role in rate of disease progression in multiple sclerosis.
abstract: Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important mediator of immune responses and inflammation is interleukin-6 (IL-6). Previously, elevated levels of IL-6 in mononuclear cells in blood and in brain tissue from MS patients have been reported. Various polymorphisms in the promoter region of the IL6 gene have also been linked with IL-6 protein levels. In MS, several small studies have investigated whether two IL6 promoter polymorphisms (-597 G>A and -174 G>C) correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (-572 G>C) in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different -597 or -174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position -572, although this was not significant after correction for multiple comparisons. Interestingly, however, the -572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression.
authors.affiliation: The University of Queensland, Centre for Clinical Research, Royal Brisbane & Women's Hospital, 4029 Brisbane, Australia. j.yan@uq.edu.au.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Clement Yihao
authors.initials: CY
authors.lastname: Lin
authors.forename: Peter A
authors.initials: PA
authors.lastname: Csurhes
authors.forename: Michael P
authors.initials: MP
authors.lastname: Pender
authors.forename: Pamela A
authors.initials: PA
authors.lastname: McCombe
authors.forename: Judith M
authors.initials: JM
authors.lastname: Greer
mesh_terms: D000328:Adult; D000483:Alleles; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index
chemical_list: D006680:HLA Antigens; D015850:Interleukin-6