Abstract
Chronic kidney disease (CKD) has a prevalence of approximately 10% in adult populations. CKD can progress to end-stage renal disease (ESRD) and this is usually fatal unless some form of renal replacement therapy (chronic dialysis or renal transplantation) is provided. There is an inherited predisposition to CKD with several genetic risk markers now identified. The UMOD gene has been associated with CKD of varying aetiologies. An AmpliSeq next generation sequencing panel was developed to facilitate comprehensive sequencing of the UMOD gene, covering exonic and regulatory regions. SNPs and CpG sites in the genomic region encompassing UMOD were evaluated for association with CKD in two studies; the UK Wellcome Trust Case-Control 3 Renal Transplant Dysfunction Study (n = 1088) and UK-ROI GENIE GWAS (n = 1726). A technological comparison of two Ion Torrent machines revealed 100% allele call concordance between S5 XL™ and PGM™ machines. One SNP (rs183962941), located in a non-coding region of UMOD, was nominally associated with ESRD (p = 0.008). No association was identified between UMOD variants and estimated glomerular filtration rate. Analysis of methylation data for over 480,000 CpG sites revealed differential methylation patterns within UMOD, the most significant of these was cg03140788 p = 3.7 x 10−10.
Highlights
Chronic kidney disease (CKD) is defined by sustained and often progressive decrease in renal function which is generally irreversible
Renal function is most commonly measured by analysis of the serum creatinine concentration and calculating an estimated glomerular filtration rate using formulae based on the individual’s age, gender, ethnicity and serum creatinine value [1]
Variants within the uromodulin protein (UMOD) gene were determined for a total for 45 individuals; 23 kidney transplant recipients with end-stage renal disease (ESRD), and 22 matching donors with no known kidney disease
Summary
Chronic kidney disease (CKD) is defined by sustained and often progressive decrease in renal function (over months to years) which is generally irreversible. Renal function is most commonly measured by analysis of the serum creatinine concentration and calculating an estimated glomerular filtration rate (eGFR) using formulae based on the individual’s age, gender, ethnicity and serum creatinine value [1]. CKD is typically asymptomatic and this can mean that diagnosis is delayed and CKD has progressed further before it is recognised [2]. With earlier diagnosis and effective management, CKD progression may be slowed or even halted [3]. CKD affects approximately 10% of adults the prevalence in older age groups is much higher [4], and CKD is strongly associated with cardiovascular disease.
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