Genetic Characteristics of Korean Patients with Autosomal Dominant Polycystic Kidney Disease by Targeted Exome Sequencing
Autosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of end-stage renal disease (ESRD). Genetic information is of the utmost importance in understanding pathogenesis of ADPKD. Therefore, this study aimed to demonstrate the genetic characteristics of ADPKD and their effects...
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Published in | Scientific reports Vol. 9; no. 1; p. 16952 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
18.11.2019
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Autosomal dominant polycystic kidney disease (ADPKD) is one of the main causes of end-stage renal disease (ESRD). Genetic information is of the utmost importance in understanding pathogenesis of ADPKD. Therefore, this study aimed to demonstrate the genetic characteristics of ADPKD and their effects on renal function in 749 Korean ADPKD subjects from 524 unrelated families. Genetic studies of
PKD1/2
were performed using targeted exome sequencing combined with Sanger sequencing in exon 1 of the
PKD1
gene and a multiple ligation probe assay. The mutation detection rate was 80.7% (423/524 families, 331 mutations) and 70.7% was novel.
PKD1
protein-truncating (
PKD1
-PT) genotype was associated with younger age at diagnosis, larger kidney volume, lower renal function compared to
PKD1
non-truncating and
PKD2
genotypes. The
PKD1
genotype showed earlier onset of ESRD compared to
PKD2
genotype (64.9 vs. 72.9 years old, P < 0.001). In frailty model controlled for age, gender, and familial clustering effect,
PKD2
genotype had 0.2 times lower risk for reaching ESRD than
PKD1
-PT genotype (p = 0.037). In conclusion, our results suggest that genotyping can contribute to selecting rapid progressors for new emerging therapeutic interventions among Koreans. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-019-52474-1 |