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Kim, Kwangwoo,Brown, Elizabeth E,Choi, Chan-Bum,Alarc?n-Riquelme, Marta E,Kelly, Jennifer A,Glenn, Stuart B,Ojwang, Joshua O,Adler, Adam,Lee, Hye-Soon,Boackle, Susan A,Criswell, Lindsey A,Alarc?n, Gra British Medical Association 2012 Annals of the Rheumatic Diseases Vol.71 No.11
<P>Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin α(M) (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM.</P>
Lessard, Christopher J.,Adrianto, Indra,Kelly, Jennifer A.,Kaufman, Kenneth M.,Grundahl, Kiely M.,Adler, Adam,Williams, Adrienne H.,Gallant, Caroline J.,Anaya, Juan-Manuel,Bae, Sang-Cheol,Boackle, Sus Elsevier 2011 American journal of human genetics Vol.88 No.1
<P>Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10<SUP>−8</SUP>) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between <I>PDHX</I> and <I>CD44</I> showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10<SUP>−8</SUP>, OR = 0.83) and rs387619 (p = 7.7 × 10<SUP>−7</SUP>, OR = 0.83) in the European samples with p<SUB>meta</SUB> = 1.82 × 10<SUP>−9</SUP> for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10<SUP>−3</SUP>, OR = 0.81 and p = 4.3 × 10<SUP>−4</SUP>, OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p<SUB>meta</SUB> = 2.36 × 10<SUP>−13</SUP>. This locus contains multiple regulatory sites that could potentially affect expression and functions of <I>CD44</I>, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.</P>