Title

Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes.

Document Type

Article

Publication Date

7-14-2021

Publication Title

Journal of the American Society of Nephrology : JASN

Keywords

JMG

JAX Source

J Am Soc Nephrol 2021 Jul 14 [online ahead of print]

ISSN

1533-3450

PMID

34261756

DOI

https://doi.org/10.1681/asn.2020101457

Abstract

BACKGROUND: Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of end stage kidney disease (ESKD) in individuals with type 1 diabetes at advanced kidney disease stage.

METHODS: Gene-based exome array analysis of 15,449 genes in 5 large incidence cohorts of individuals with type 1 diabetes and proteinuria were analyzed for survival time-to-ESKD, testing the top gene in a 6th cohort (N=2,372/1,115 events all cohorts) and replicating in two retrospective case-control studies (N=1,072 cases, 752 controls). Deep resequencing of the top associated gene in 5 cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models.

RESULTS: Protein coding variants in the hydroxysteroid 17-beta dehydrogenase 14 gene (

CONCLUSIONS:

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