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Human Molecular Genetics Advance Access published online on March 13, 2009
Human Molecular Genetics, 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 Hirankarn2, Chak Sing Lau3,#, Chi Chiu Mok4, Tak Mao Chan3, Raymond W.S. Wong3, Ka Wing Lee5, Mo Yin Mok3, Sik Nin Wong6, Yingyos Avihingsanon7, Irene Oi Lin Ng8, Tsz Leung Lee1, Marco Hok Kung Ho1, Pamela Pui Wah Lee1, Wilfred Hing Sang Wong1, Pak Chung Sham9 and Yu Lung Lau1,*

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

* Correspondence to: Yu Lung Lau, M. D., Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine and Queen Mary Hospital, The University of Hong Kong, Hong Kong, China Tel: (852) 2855 4481 Fax: (852) 2855 1523eee 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 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 nonsynonymous 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.

# Current address: Division of Medicine & Therapeutics, Ninewells Hospital & Medical School, Dundee, DD1 9SY, Tayside, UK


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