Publication Date:
2010-07-22
Description:
African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980843/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980843/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Genovese, Giulio -- Friedman, David J -- Ross, Michael D -- Lecordier, Laurence -- Uzureau, Pierrick -- Freedman, Barry I -- Bowden, Donald W -- Langefeld, Carl D -- Oleksyk, Taras K -- Uscinski Knob, Andrea L -- Bernhardy, Andrea J -- Hicks, Pamela J -- Nelson, George W -- Vanhollebeke, Benoit -- Winkler, Cheryl A -- Kopp, Jeffrey B -- Pays, Etienne -- Pollak, Martin R -- HHSN261200800001E/PHS HHS/ -- K08-DK076868/DK/NIDDK NIH HHS/ -- R01 DK 070941/DK/NIDDK NIH HHS/ -- R01 DK 084149/DK/NIDDK NIH HHS/ -- R01 DK053591/DK/NIDDK NIH HHS/ -- R01 DK054931/DK/NIDDK NIH HHS/ -- R01 DK054931-12/DK/NIDDK NIH HHS/ -- R01 DK054931-13/DK/NIDDK NIH HHS/ -- R01 DK066358/DK/NIDDK NIH HHS/ -- R01 DK070941/DK/NIDDK NIH HHS/ -- R01 DK084149/DK/NIDDK NIH HHS/ -- R01 DK54931/DK/NIDDK NIH HHS/ -- R01HL56266/HL/NHLBI NIH HHS/ -- Z01 DK043308/DK/NIDDK NIH HHS/ -- Z01 DK043308-12/Intramural NIH HHS/ -- ZIA BC 010022/BC/NCI NIH HHS/ -- New York, N.Y. -- Science. 2010 Aug 13;329(5993):841-5. doi: 10.1126/science.1193032. Epub 2010 Jul 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20647424" target="_blank"〉PubMed〈/a〉
Keywords:
Africa
;
African Americans/*genetics
;
Alleles
;
Apolipoproteins/blood/*genetics/metabolism
;
Case-Control Studies
;
Cohort Studies
;
Gene Frequency
;
Genetic Association Studies
;
Genetic Predisposition to Disease
;
Glomerulosclerosis, Focal Segmental/ethnology/*genetics
;
Haplotypes
;
Humans
;
Hypertension/complications
;
Immunity, Innate
;
Kidney Failure, Chronic/ethnology/etiology/*genetics
;
Linkage Disequilibrium
;
Lipoproteins, HDL/blood/*genetics/metabolism
;
Logistic Models
;
Molecular Motor Proteins/genetics
;
Myosin Heavy Chains/genetics
;
*Polymorphism, Single Nucleotide
;
Recombinant Proteins/metabolism
;
Selection, Genetic
;
Sequence Deletion
;
Trypanosoma brucei rhodesiense/*metabolism
;
Trypanosomiasis, African/genetics/parasitology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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