title: The influence of non-HLA gene polymorphisms and interactions on disease risk in a Western Australian multiple sclerosis cohort.
abstract: Non-Human Leukocyte Antigen (HLA) genes have concomitant, although modest, effects on multiple sclerosis (MS) susceptibility; however findings have varied in different populations. Here we present the results of an association study of 16 single nucleotide polymorphisms (SNPs) in 10 non-HLA genes (IL7R, IL2RA, CLEC-16A, TYK2, CD58, IRF5, STAT3, CTLA-4, APOE, ICAM-1) in a Western Australian cohort of 350 MS patients and 498 population control subjects. Our results indicate that in this population, SNPs in IL7R, TYK2, IRF5 and APOE have modifying effects on MS susceptibility. We also found evidence of interactive protective effects between polymorphisms in the IL7R/CD58, CLEC-16A/CTLA-4, and TYK2/IRF5 genes, which in some instances are restricted within HLA- or gender-defined groups.
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.forename: Kym
authors.initials: K
authors.lastname: Pham
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.forename: David
authors.initials: D
authors.lastname: Nolan
authors.forename: Allison
authors.initials: A
authors.lastname: Castley
authors.forename: Frank T
authors.initials: FT
authors.lastname: Christiansen
authors.forename: Petra
authors.initials: P
authors.lastname: Czarniak
authors.forename: Yuebei
authors.initials: Y
authors.lastname: Luo
authors.forename: Jingshan
authors.initials: J
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Garlepp
authors.forename: Steve
authors.initials: S
authors.lastname: Wilton
authors.forename: William M
authors.initials: WM
authors.lastname: Carroll
authors.forename: Frank L
authors.initials: FL
authors.lastname: Mastaglia
authors.forename: Allan G
authors.initials: AG
authors.lastname: Kermode
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology; D012042:Registries; D012307:Risk Factors; D014904:Western Australia / Q000453:epidemiology
chemical_list: D006680:HLA Antigens
keywords: APOE; Apolipoprotein E; C-type lectin domain family 16; CLEC-16A; CTLA-4; Cytotoxic T-lymphocyte antigen 4; HLA; ICAM-1; IL2RA; IL7R; IRF5; Intercellular adhesion molecule 1; Interferon regulatory factor 5; Interleukin 2 receptor a; Interleukin 7 receptor; Multiple sclerosis; Non-HLA genes; STAT3; Signal transducer and activator of transcription 3; Single nucleotide polymorphisms; TYK2; Tyrosine kinase 2