Genetic loci associated with renal function measures and chronic kidney disease in children: the Pediatric Investigation for Genetic Factors Linked with Renal Progression Consortium

被引：31

作者：

Wuttke, Matthias ^{[1
]}

Wong, Craig S. ^{[2
]}

Wuehl, Elke ^{[3
]}

Epting, Daniel ^{[1
]}

Luo, Li ^{[4
]}

Hoppmann, Anselm ^{[1
]}

Doyon, Anke ^{[3
]}

Li, Yong ^{[1
]}

Sozeri, Betul ^{[5
]}

Thurn, Daniela ^{[6
]}

Helmstadter, Martin ^{[1
]}

Huber, Tobias B. ^{[1
]}

Blydt-Hansen, Tom D. ^{[7
]}

Kramer-Zucker, Albrecht ^{[1
]}

Mehls, Otto ^{[3
]}

Melk, Anette ^{[6
]}

Querfeld, Uwe ^{[8
]}

Furth, Susan L. ^{[9
,10
]}

Warady, Bradley A. ^{[11
]}

Schaefer, Franz ^{[3
]}

Koettgen, Anna ^{[1
,12
]}

机构：

[1] Univ Freiburg, Med Ctr, Dept Internal Med, Div Renal, Hugstetter Str 55, D-79106 Freiburg, Germany

[2] Univ New Mexico, Childrens Hosp, Div Pediat Nephrol, Albuquerque, NM 87131 USA

[3] Univ Med Ctr Heidelberg, Div Pediat Nephrol, Heidelberg, Germany

[4] Univ New Mexico, Dept Internal Med, Div Epidemiol, Albuquerque, NM 87131 USA

[5] Ege Univ, Fac Med, Izmir, Turkey

[6] Hannover Med Sch, Dept Pediat Nephrol, Hannover, Germany

[7] Univ Manitoba, Winnipeg, MB, Canada

[8] Charite, D-13353 Berlin, Germany

[9] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[10] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Epidemiol, Philadelphia, PA 19104 USA

[11] Childrens Mercy Hosp, Div Pediat Nephrol, Kansas City, MO 64108 USA

[12] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

来源：

NEPHROLOGY DIALYSIS TRANSPLANTATION | 2016年 / 31卷 / 02期

关键词：

pediatric chronic kidney disease; genetic epidemiology; genome-wide association study; glomerular filtration rate; proteinuria; GENOME-WIDE ASSOCIATION; POPULATION; EPIDEMIOLOGY; VARIANTS; DESIGN; FAILURE; LIFE; GFR;

D O I：

10.1093/ndt/gfv342

中图分类号：

R3 [基础医学]; R4 [临床医学];

学科分类号：

1001 ; 1002 ; 100602 ;

摘要：

Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown. The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular Comorbidity in Children with CKD (4C). Clean genotype data from > 10 million genotyped or imputed single-nucleotide polymorphisms (SNPs) were available for 1136 patients with measurements of serum creatinine at study enrolment. Genome-wide association studies were conducted to relate the SNPs to creatinine-based estimated glomerular filtration rate (eGFR(crea)) and proteinuria (urinary albumin- or protein-to-creatinine ratio a parts per thousand yen300 and a parts per thousand yen500 mg/g, respectively). In addition, European-ancestry PediGFR patients (cases) were compared with 1347 European-ancestry children without kidney disease (controls) to identify genetic variants associated with the presence of CKD. SNPs with suggestive association P-values < 1x10(-5) were identified in 10 regions for eGFR(crea), four regions for proteinuria and six regions for CKD including some plausible biological candidates. No SNP was associated at genome-wide significance (P < 5x10(-8)). Investigation of the candidate genes for proteinuria in adults from the general population provided support for a region on chromosome 15 near RSL24D1/UNC13C/RAB27A. Conversely, targeted investigation of genes harboring GFR-associated variants in adults from the general population did not reveal significantly associated SNPs in children with CKD. Our findings suggest that larger collaborative efforts will be needed to draw reliable conclusions about the presence and identity of common variants associated with eGFR, proteinuria and CKD in pediatric populations.

引用

页码：262 / 269

页数：8

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