title: ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai.
abstract: ITGAM was recently found to be associated with systemic lupus erythematosus (SLE) in populations of not only European ancestry, but also in Hispanic- and African-Americans, Mexicans and Colombians. The risk alleles in the gene, however, were found to be monomorphic in two Asian populations examined: Japanese and Korean. In this study, using a collection of 910 SLE patients and 2360 controls from Chinese living in Hong Kong, analyzed by both genome-wide association and direct sequencing, we confirmed the association of the same risk alleles in ITGAM with the disease. These findings were further replicated in the Thai population with 278 patients and 383 ethnicity- and geography-matched controls. Subphenotype stratification analyses showed significantly more involvement of the gene in patients with renal nephritis and neurological disorders. Although our results support a pivotal role by rs1143679 (R77H) in disease association, our data also suggests an additional contribution from rs1143683, another non-synonymous polymorphism in this gene (A858V). Therefore, despite the low-allele frequencies of the risk alleles of the gene in our two Asian populations, ITGAM was confirmed to be a risk factor related to disease susceptibility and probably severe manifestations of SLE.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong.
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhao
authors.forename: Nattiya
authors.initials: N
authors.lastname: Hirankarn
authors.forename: Chak Sing
authors.initials: CS
authors.lastname: Lau
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Mok
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.forename: Raymond W S
authors.initials: RW
authors.lastname: Wong
authors.forename: Ka Wing
authors.initials: KW
authors.lastname: Lee
authors.forename: Mo Yin
authors.initials: MY
authors.lastname: Mok
authors.forename: Sik Nin
authors.initials: SN
authors.lastname: Wong
authors.forename: Yingyos
authors.initials: Y
authors.lastname: Avihingsanon
authors.forename: Irene Oi
authors.initials: IO
authors.lastname: Lin
authors.forename: Tsz Leung
authors.initials: TL
authors.lastname: Lee
authors.forename: Marco Hok Kung
authors.initials: MH
authors.lastname: Ho
authors.forename: Pamela Pui Wah
authors.initials: PP
authors.lastname: Lee
authors.forename: Wilfred Hing Sang
authors.initials: WH
authors.lastname: Wong
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D039481:CD11b Antigen / Q000235:genetics*; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D055106:Genome-Wide Association Study; D006723:Hong Kong; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013785:Thailand; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human