Abstract
The familial clustering observed in chronic kidney disease of uncertain etiology (CKDu) characterized by tubulointerstitial damages in the North Central Region of Sri Lanka strongly suggests the involvement of genetic factors in its pathogenesis. The objective of the present study is to use whole-exome sequencing to identify the genetic variants associated with CKDu. Whole-exome sequencing of eight CKDu cases and eight controls was performed, followed by direct sequencing of candidate loci in 301 CKDu cases and 276 controls. Association study revealed rs34970857 (c.658G>A/p.V220M) located in the KCNA10 gene encoding a voltage-gated K channel as the most promising SNP with the highest odds ratio of 1.74. Four rare variants were identified in gene encoding Laminin beta2 (LAMB2) which is known to cause congenital nephrotic syndrome. Three out of four variants in LAMB2 were novel variants found exclusively in cases. Genetic investigations provide strong evidence on the presence of genetic susceptibility for CKDu. Possibility of presence of several rare variants associated with CKDu in this population is also suggested.
Highlights
Chronic kidney disease (CKD) is a global public health issue due to increasing prevalence and economic burden incurred [1,2,3]
Objectives The familial clustering observed in chronic kidney disease of uncertain etiology (CKDu) characterized by tubulointerstitial damages in the North Central Region of Sri Lanka strongly suggests the involvement of genetic factors in its pathogenesis
Four rare variants were identified in gene encoding Laminin beta2 (LAMB2) which is known to cause congenital nephrotic syndrome
Summary
Chronic kidney disease (CKD) is a global public health issue due to increasing prevalence and economic burden incurred [1,2,3]. This has been attributed to an increasing incidence of conventional risk factors such as diabetes and hypertension in populations around the world. Aturaliya and coworkers reported that major risk factors for CKD could not be identified for 87 % of these CKD patients through the available diagnostic tests of the time. This entity characterized by tubulointerstitial damages has since been termed CKD of uncertain etiology (CKDu) [5]
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