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Evaluation of <i>TRAF6</i> in a large multiancestral lupus cohort
Namjou, Bahram,Choi, Chan‐,Bum,Harley, Isaac T. W.,Alarcó,n‐,Riquelme, Marta E.,Kelly, Jennifer A.,Glenn, Stuart B.,Ojwang, Joshua O.,Adler, Adam,Kim, Kwangwoo,Gallant, Caroline J.,B Wiley Subscription Services, Inc., A Wiley Company 2012 Vol.64 No.6
<P><B>Abstract</B></P><P><B>Objective</B></P><P>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of <I>TRAF6</I> as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development.</P><P><B>Methods</B></P><P>Fifteen single‐nucleotide polymorphisms (SNPs) across <I>TRAF6</I> were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population‐based case–control association analyses and meta‐analyses were performed. <I>P</I> values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.</P><P><B>Results</B></P><P>Evidence of associations was detected in multiple SNPs. The best overall <I>P</I> values were obtained for SNPs rs5030437 and rs4755453 (<I>P</I> = 7.85 × 10<SUP>−5</SUP> and <I>P</I> = 4.73 × 10<SUP>−5</SUP>, respectively) without significant heterogeneity among populations (<I>P</I> = 0.67 and <I>P</I> = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r<SUP>2</SUP> = 0.95) and demonstrated evidence of association with SLE in the same direction (meta‐analysis <I>P</I> = 9.15 × 10<SUP>−4</SUP>, OR 0.89 [95% CI 0.83–0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta‐analysis <I>P</I> = 1.99 × 10<SUP>−6</SUP>, OR 0.57 [95% CI 0.45–0.72], for rs5030470). Finally, evidence of family‐based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (<I>P</I> = 0.02) under a dominant model.</P><P><B>Conclusion</B></P><P>Our data indicate the presence of association of <I>TRAF6</I> with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of <I>TRAF6</I> in the pathogenesis of autoimmunity.</P>
Heo, Yun-Jeong,Chung, In-Young,Choi, Kelly B.,Lau, Gee W.,Cho, You-Hee Microbiology Society 2007 Microbiology Vol.153 No.9
<P>A temperate transposable bacteriophage (MP22) was isolated from a Korean clinical isolate of Pseudomonas aeruginosa. It has a coliphage lambda-like morphology and a double-stranded DNA genome. The complete nucleotide sequence and annotation of the MP22 genome and its characteristics are presented. The MP22 genome is 36 409 bp long with a G+C content of 64.2 mol%. The genome contains 51 proposed ORFs, of which 48 (94 %) display synteny and significant nucleotide and protein sequence similarity to the corresponding ORFs of the closely related phage, D3112. Three of the predicted ORFs are unique proteins, whose functions are yet to be revealed. The phage c repressors exhibit striking dissimilarities and, when present as a single gene, did not show cross-immunity. In contrast, although an MP22 lysogen could be productively infected with D3112, MP22 could not grow on a D3112 lysogen, indicating a role of other D3112 genes in superinfection exclusion.</P>
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>