Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014:2014:305436.
doi: 10.1155/2014/305436. Epub 2014 Feb 18.

Evaluation of SLE Susceptibility Genes in Malaysians

Julio E Molineros  1 , Kek Heng Chua  2 , Celi Sun  1 , Lay Hoong Lian  3 , Prasenjeet Motghare  1 , Xana Kim-Howard  1 , Swapan K Nath  1
Affiliations

Evaluation of SLE Susceptibility Genes in Malaysians

Julio E Molineros et al. Autoimmune Dis. 2014.

Abstract

Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous autoimmune disease with strong genetic and environmental components. Our objective was to replicate 25 recently identified SLE susceptibility genes in two distinct populations (Chinese (CH) and Malays (MA)) from Malaysia. We genotyped 347 SLE cases and 356 controls (CH and MA) using the ImmunoChip array and performed an admixture corrected case-control association analysis. Associated genes were grouped into five immune-related pathways. While CH were largely homogenous, MA had three ancestry components (average 82.3% Asian, 14.5% European, and 3.2% African). Ancestry proportions were significantly different between cases and controls in MA. We identified 22 genes with at least one associated SNP (P < 0.05). The strongest signal was at HLA-DRA (P Meta = 9.96 × 10(-9); P CH = 6.57 × 10(-8), P MA = 6.73 × 10(-3)); the strongest non-HLA signal occurred at STAT4 (P Meta = 1.67 × 10(-7); P CH = 2.88 × 10(-6), P MA = 2.99 × 10(-3)). Most of these genes were associated with B- and T-cell function and signaling pathways. Our exploratory study using high-density fine-mapping suggests that most of the established SLE genes are also associated in the major ethnicities of Malaysia. However, these novel SNPs showed stronger association in these Asian populations than with the SNPs reported in previous studies.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Principal components analysis of Chinese and Malay cohorts. Notably the Malaysian Chinese were a more homogeneous population than the Malays (CEU: North Europeans from CEPH; CHB: Beijing Chinese; JPT: Japanese; YRI: Yorubans from Nigeria).
Figure 2
Figure 2
Admixture proportions of Chinese and Malays. Malaysian Chinese had less evidence of admixture from Europeans and Africans than Malaysian Malays (CH: Malaysian Chinese; MA: Malaysian Malays; CEU: North Europeans from CEPH; CHB: Beijing Chinese; JPT: Japanese; YRI: Yorubans from Nigeria).
Figure 3
Figure 3
Comparison of allele frequencies of the top 25 SNPs from CH versus HapMap Chinese from Beijing (CHB) and MA versus CHB.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Mok MY, Li WL. Do Asian patients have worse lupus? Lupus. 2010;19(12):1384–1390. - PubMed
    1. Kelley JM, Edberg JC, Kimberly RP. Pathways: strategies for susceptibility genes in SLE. Autoimmunity Reviews. 2010;9(7):473–476. - PMC - PubMed
    1. Deng Y, Tsao BP. Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nature Reviews Rheumatology. 2010;6(12):683–692. - PMC - PubMed
    1. Sestak AL, Fürnrohr BG, Harley JB, Merrill JT, Namjou B. The genetics of systemic lupus erythematosus and implications for targeted therapy. Annals of the Rheumatic Diseases. 2011;70(supplement 1):i37–i43. - PubMed
    1. Harley JB, Alarcón-Riquelme ME, Criswell LA, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nature Genetics. 2008;40(2):204–210. - PMC - PubMed