Apolipoprotein L1 (APOL1) risk variant toxicity depends on the haplotype background

被引：45

作者：

Lannon, Herbert ^{[1
]}

Shah, Shrijal S. ^{[1
]}

Dias, Leny ^{[1
]}

Blackler, Daniel ^{[1
]}

Alper, Seth L. ^{[1
,2
]}

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

Friedman, David J. ^{[1
]}

机构：

[1] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, 330 Brookline Ave, Boston, MA 02215 USA

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

来源：

KIDNEY INTERNATIONAL | 2019年 / 96卷 / 06期

基金：

美国国家卫生研究院;

关键词：

APOL1; chronic kidney disease; focal segmental glomerulosclerosis; haplotype; trypanosome; KIDNEY-DISEASE; INJURY;

D O I：

10.1016/j.kint.2019.07.010

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

The Apolipoprotein L1 (APOL1) risk variants G1 and G2 are associated with high rates of kidney disease in African Americans in genetic studies. However, our understanding of APOL1 biology has lagged far behind. Here we report that engineering G1 and G2 mutations on unnatural haplotype backgrounds instead of on the specific G1 and G2 haplotype backgrounds that occur in nature profoundly alters APOL1-mediated cytotoxicity in experimental systems. Thus, in addition to helping resolve some important controversies in the APOL1 field, our demonstration of the critical influence of haplotype background may apply more generally to the study of other genetic variants that cause or predispose to human disease.

引用

页码：1303 / 1307

页数：5

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