Journal article
End-Stage Renal Disease in African Americans With Lupus Nephritis Is Associated With APOL1
Arthritis & rheumatology (Hoboken, N.J.), Vol.66(2), pp.390-396
02/2014
DOI: 10.1002/art.38220
PMCID: PMC4002759
PMID: 24504811
Abstract
Objective. Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that exhibits familial aggregation and may progress to end-stage renal disease (ESRD). LN is more prevalent among African Americans than among European Americans. This study was undertaken to investigate the hypothesis that the apolipoprotein L1 gene (APOL1) nephropathy risk alleles G1/G2, common in African Americans and rare in European Americans, contribute to the ethnic disparity in risk.
Methods. APOL1 G1 and G2 nephropathy alleles were genotyped in 855 African American SLE patients with LN-ESRD (cases) and 534 African American SLE patients without nephropathy (controls) and tested for association under a recessive genetic model, by logistic regression.
Results. Ninety percent of the SLE patients were female. The mean +/- SD age at SLE diagnosis was significantly lower in LN-ESRD cases than in SLE non-nephropathy controls (27.3 +/- 10.9 years versus 39.5 +/- 12.2 years). The mean +/- SD time from SLE diagnosis to development of LN-ESRD in cases was 7.3 +/- 7.2 years. The G1/G2 risk alleles were strongly associated with SLE-ESRD, with 25% of cases and 12% of controls having 2 nephropathy alleles (odds ratio [OR] 2.57, recessive model P = 1.49 x 10(-9)), and after adjustment for age, sex, and ancestry admixture (OR 2.72, P = 6.23 x 10(-6)). The age-, sex-, and admixture-adjusted population attributable risk for ESRD among patients with G1/G2 polymorphisms was 0.26, compared to 0.003 among European American patients. The mean time from SLE diagnosis to ESRD development was similar to 2 years earlier among individuals with APOL1 risk genotypes (P = 0.01).
Conclusion. APOL1 G1/G2 alleles strongly impact the risk of LN-ESRD in African Americans, as well as the time to progression to ESRD. The high frequency of these alleles in African Americans with near absence in European Americans explains an important proportion of the increased risk of LN-ESRD in African Americans.
Details
- Title: Subtitle
- End-Stage Renal Disease in African Americans With Lupus Nephritis Is Associated With APOL1
- Creators
- Barry I. Freedman - Wake Forest UniversityCarl D. Langefeld - Wake Forest UniversityKelly K. Andringa - University of Alabama at BirminghamJennifer A. Croker - University of Alabama at BirminghamAdrienne H. Williams - Wake Forest UniversityNeva E. Garner - University of Alabama at BirminghamDaniel J. Birmingham - The Ohio State UniversityLee A. Hebert - The Ohio State UniversityPamela J. Hicks - Wake Forest UniversityMark S. Segal - University of FloridaJeffrey C. Edberg - University of Alabama at BirminghamElizabeth E. Brown - University of Alabama at BirminghamGraciela S. Alarcon - University of Alabama at BirminghamKaren H. Costenbader - Brigham and Women's HospitalMary E. Comeau - Wake Forest UniversityLindsey A. Criswell - University of California, San FranciscoJohn B. Harley - Cincinnati Children's Hospital Medical CenterJudith A. James - University of OklahomaDiane L. Kamen - Medical University of South CarolinaS. Sam Lim - Emory UniversityJoan T. Merrill - Oklahoma Medical Research FoundationKathy L. Sivils - Oklahoma Medical Research FoundationTimothy B. Niewold - Mayo Clinic in ArizonaNeha M. Patel - Suny Downstate Med Ctr, Brooklyn, NY 11203 USAMichelle Petri - Johns Hopkins UniversityRosalind Ramsey-Goldman - Northwestern UniversityJohn D. Reveille - The University of Texas Health Science Center at HoustonJane E. Salmon - Hospital for Special SurgeryBetty P. Tsao - University of California, Los AngelesKeisha L. Gibson - University of North Carolina at Chapel HillJoyce R. Byers - Wake Forest UniversityAnna K. Vinnikova - Virginia Commonwealth UniversityJanice P. Lea - Emory UniversityBruce A. Julian - University of Alabama at BirminghamRobert P. Kimberly - University of Alabama at BirminghamLupus Nephritis–End-Stage Renal Disease Consortium
- Resource Type
- Journal article
- Publication Details
- Arthritis & rheumatology (Hoboken, N.J.), Vol.66(2), pp.390-396
- DOI
- 10.1002/art.38220
- PMID
- 24504811
- PMCID
- PMC4002759
- NLM abbreviation
- Arthritis Rheumatol
- ISSN
- 2326-5191
- eISSN
- 2326-5205
- Publisher
- Wiley
- Number of pages
- 7
- Grant note
- PO094002 / US Department of Defense; United States Department of Defense U01AI101934 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) US Department of Veterans Affairs Alliance for Lupus Research P60AR062755 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) UL1TR001079 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) James D. Casto Research Fund I01BX001834 / Veterans Affairs; US Department of Veterans Affairs Mary Kirkland Center for Lupus Research Kirkland Scholar Award P30DK042086 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) UL1RR025741 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) P30GM103510 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) UL1-RR-029882; R01-AR-060861; K08-AI-083790; P30-DK-42086; L30-AI-071651; UL1-RR-024999; R01-AR-043727; K24-AR-002138; P60-AR-30692; UL1-RR-025741; R01-AR-043814; RC2-AR-058951; UL1-TR-000165; P01-AR-049084; P01-AI-083194 / NIH.; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Lupus Research Institute Genzyme; Sanofi-Aventis; Genzyme Corporation Biogen Idec; Biogen R01-DK-070941; DK-084149; P01-DK-55546; UL1-RR-025755; P60-AR-053308; K24-AR-02175; R01-AR-052300; UL1-TR-000004; AI-024717; AI-083194; AR-049084; AR-042460; U191082714; P30-AR-053483; P30-GM-103510; U01-AI-101934; P60-AR-062755 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Astellas Pharma; Astellas Pharmaceuticals
- Language
- English
- Date published
- 02/2014
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984548857802771
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