Molineros Julio E, Chua Kek Heng, Sun Celi, Lian Lay Hoong, Motghare Prasenjeet, Kim-Howard Xana, Nath Swapan K
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 1025 NE 13th Street, Oklahoma City, OK 73104, USA.
Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Autoimmune Dis. 2014;2014:305436. doi: 10.1155/2014/305436. Epub 2014 Feb 18.
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.
系统性红斑狼疮（SLE）是一种临床异质性自身免疫性疾病，具有强大的遗传和环境因素。我们的目标是在来自马来西亚的两个不同人群（华人（CH）和马来人（MA））中复制25个最近鉴定出的SLE易感基因。我们使用免疫芯片阵列对347例SLE病例和356名对照（CH和MA）进行基因分型，并进行了混合校正的病例对照关联分析。相关基因被分为五个免疫相关途径。虽然CH人群基本同质，但MA人群有三个祖先成分（平均82.3%亚洲人、14.5%欧洲人和3.2%非洲人）。MA人群中病例和对照的祖先比例存在显著差异。我们鉴定出22个至少有一个相关单核苷酸多态性（SNP）的基因（P < 0.05）。最强信号出现在HLA-DRA（P Meta = 9.96 × 10(-9)；P CH = 6.57 × 10(-8)，P MA = 6.73 × 10(-3)）；最强的非HLA信号出现在STAT4（P Meta = 1.67 × 10(-7)；P CH = 2.88 × 10(-6)，P MA = 2.99 × 10(-3)）。这些基因大多与B细胞和T细胞功能及信号通路相关。我们使用高密度精细定位的探索性研究表明，大多数已确定的SLE基因在马来西亚的主要种族中也存在关联。然而，这些新的SNP在这些亚洲人群中显示出比先前研究报道的SNP更强的关联性。
