ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai.
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.
Yang
Wanling
W
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong.
Zhao
Minghui
M
Hirankarn
Nattiya
N
Lau
Chak Sing
CS
Mok
Chi Chiu
CC
Chan
Tak Mao
TM
Wong
Raymond W S
RW
Lee
Ka Wing
KW
Mok
Mo Yin
MY
Wong
Sik Nin
SN
Avihingsanon
Yingyos
Y
Lin
Irene Oi
IO
Lee
Tsz Leung
TL
Ho
Marco Hok Kung
MH
Lee
Pamela Pui Wah
PP
Wong
Wilfred Hing Sang
WH
Sham
Pak Chung
PC
Lau
Yu Lung
YL
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
D039481:CD11b Antigen; C509295:ITGAM protein, human