Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans

被引：1501

作者：

Genovese, Giulio ^{[1
,2
,3
]}

Friedman, David J. ^{[1
,2
,4
]}

Ross, Michael D. ^{[5
]}

Lecordier, Laurence ^{[6
]}

Uzureau, Pierrick ^{[6
]}

Freedman, Barry I. ^{[7
]}

Bowden, Donald W. ^{[8
,9
,10
]}

Langefeld, Carl D. ^{[10
,11
,12
]}

Oleksyk, Taras K. ^{[13
]}

Knob, Andrea L. Uscinski ^{[5
]}

Bernhardy, Andrea J. ^{[1
,2
]}

Hicks, Pamela J. ^{[8
,9
,10
]}

Nelson, George W. ^{[14
]}

Vanhollebeke, Benoit ^{[6
]}

Winkler, Cheryl A. ^{[15
]}

Kopp, Jeffrey B. ^{[14
]}

Pays, Etienne ^{[6
]}

Pollak, Martin R. ^{[1
,2
,16
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Boston, MA 02215 USA

[3] Dartmouth Coll, Dept Math, Hanover, NH 03755 USA

[4] Beth Israel Deaconess Med Ctr, Dept Med, Vasc Biol Res Ctr, Boston, MA 02215 USA

[5] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02215 USA

[6] Univ Libre Bruxelles, Inst Biol & Med Mol, Mol Parasitol Lab, B-6041 Gosselies, Belgium

[7] Wake Forest Univ, Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC 27157 USA

[8] Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA

[9] Wake Forest Univ, Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA

[10] Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27157 USA

[11] Wake Forest Univ, Sch Med, Ctr Publ Hlth Genom, Dept Biostat Sci, Winston Salem, NC 27157 USA

[12] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA

[13] Univ Puerto Rico, Dept Biol, Mayaguez, PR 00681 USA

[14] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA

[15] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA

[16] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

来源：

SCIENCE | 2010年 / 329卷 / 5993期

关键词：

STAGE RENAL-DISEASE; 9 GENE MYH9; POSITIVE SELECTION; NATURAL-SELECTION; HUMAN SERUM; POLYMORPHISMS; RHODESIENSE; GENOME;

D O I：

10.1126/science.1193032

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：841 / 845

页数：5

共 23 条

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