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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EAfrican Americans suffer from lupus-related kidney failure at higher rates compared with individuals without recent African ancestry [Byrne C et al. \u003Cem\u003EAm J Kidney Dis\u003C\/em\u003E 1994; Satko SG et al. \u003Cem\u003EKidney Int Suppl\u003C\/em\u003E 2005]. This article presents findings from A National Consortium to Explore the Genotypic Basis for End-Stage Renal Disease in Lupus [1RC2-AR058951; P01-AR049084; P01-AI083194].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ELupus Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAfrican Americans suffer from lupus-related kidney failure at higher rates compared with individuals without recent African ancestry [Byrne C et al. \u003Cem\u003EAm J Kidney Dis\u003C\/em\u003E 1994; Satko SG et al. \u003Cem\u003EKidney Int Suppl\u003C\/em\u003E 2005]. Robert P. Kimberly, MD, University of Alabama at Birmingham, Birmingham, Alabama, USA, presented findings from A National Consortium to Explore the Genotypic Basis for End-Stage Renal Disease (ESRD) in Lupus [1RC2-AR058951; P01-AR049084; P01-AI083194].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ETo untangle biological and socioeconomic factors, the researchers took a genetic approach, comparing people of African American ancestry with lupus\/ESRD to those with lupus and no nephritis.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe G1 and G2 coding variants in the apolipoprotein L1 gene (\u003Cem\u003EAPOL1\u003C\/em\u003E) are strongly and reproducibly associated with focal segmental glomerulosclerosis, HIV-associated collapsing glomerulopathy, and hypertension-attributed ESRD in African Americans [Genovese G et al. \u003Cem\u003EScience\u003C\/em\u003E 2010; Tzur S et al. \u003Cem\u003EHum Genet\u003C\/em\u003E 2010]. To explore the role of \u003Cem\u003EAPOL1\u003C\/em\u003E in lupus nephritis (LN)-related ESRD, the Consortium tested for associations between \u003Cem\u003EAPOL1\u003C\/em\u003E risk variants and LN-ESRD in a national sample of unrelated African Americans with systemic lupus erythematosus (SLE).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe sample included 668 African American subjects with LN-ESRD (456 with kidney biopsy documentation, 212 physician-reported) and 697 African American subjects with longstanding SLE lacking LN (mean duration of disease was 10.1 years). In cases with LN-ESRD, 87.1% were female, 89% received cytotoxic therapy, mean \u00b1 SD age at SLE onset was 26.6\u00b10.4 years and duration of SLE diagnosis to ESRD was 7.2\u00b10.3 years with the median at 5 years. In non-nephritis SLE subjects, 93.5% were female with SLE onset at 35.2\u00b10.8 years of age.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EContrasting all cases with and without ESRD, \u003Cem\u003EAPOL1\u003C\/em\u003E risk variants were significantly associated with LN-ESRD (OR, 2.35; 95% CI, 1.77 to 3.3; p=4.25E\u003Csup\u003E-9\u003C\/sup\u003E); significant differences in association were not observed when comparing cases with or without kidney biopsy documentation to SLE subjects without LN. The duration of SLE onset to ESRD for those with the G1\/G2 variants was 5.49\u00b10.54 years (median=4). For those without the variants, it was 7.78\u00b10.37 years (median=6; p\u0026lt;0.05).\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EThe study demonstrates strong association between both \u003Cem\u003EAPOL1\u003C\/em\u003E G1 and G2 variants and LN-associated ESRD in African Americans. It appears likely that \u003Cem\u003EAPOL1\u003C\/em\u003E G1 and G2 coding variants, which are rare in European populations, contribute to nephropathy progression in LN-ESRD, as well as other nondiabetic etiologies of ESRD. These variants and their higher prevalence in those with African ancestry may explain, in part (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E), a higher prevalence of severe LN in African Americans.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/19\/10.1\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022The Genetic Load Associated with Lupus in African Americans.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1413283888\u0022 data-figure-caption=\u0022The Genetic Load Associated with Lupus in African Americans.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/19\/10.1\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/19\/10.1\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/19\/10.1\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11696\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EThe Genetic Load Associated with Lupus in African Americans.\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003E*Source: Vaughn SE et al. \u003Cem\u003EJ Leukoc Biol\u003C\/em\u003E 2012. SNP=single-nucleotide polymorphism.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from RP Kimberly, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/19\/10.1.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzn50q\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn50q\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}