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Human Molecular Genetics Advance Access originally published online on March 13, 2009
Human Molecular Genetics 2009 18(11):2063-2070; doi:10.1093/hmg/ddp118
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© 2009. The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai

Wanling Yang1, Minghui Zhao1, Nattiya Hirankarn5, Chak Sing Lau2,{dagger}, Chi Chiu Mok7, Tak Mao Chan2, Raymond W.S. Wong2, Ka Wing Lee9, Mo Yin Mok2, Sik Nin Wong8, Yingyos Avihingsanon6, Irene Oi Lin N.G.3, Tsz Leung Lee1, Marco Hok Kung Ho1, Pamela Pui Wah Lee1, Wilfred Hing Sang Wong1, Pak Chung Sham4 and Yu Lung Lau1,*

1 Department of Paediatrics and Adolescent Medicine 2 Department of Medicine 3 Department of Pathology 4 Department of Psychiatry, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong 5 Department of Microbiology, Lupus Research Unit 6 Faculty of Medicine, Department of Medicine, Chulalongkorn University, Rama 4 Road, Bangkok 10330, Thailand 7 Department of Medicine 8 Department of Paediatrics and Adolescent Medicine, Tuen Mun Hospital, New Territory, Hong Kong 9 Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong

* To whom correspondence should be addressed. Tel: +86 85228554481; Fax: +86 85228551523; Email: lauylung{at}hkucc.hku.hk

Received January 22, 2009; Revised March 3, 2009; Accepted March 10, 2009

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.

{dagger} Present address: Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Tayside, UK.


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