title: Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Dental Research, Faculty of Dentistry, University of Sydney, Sydney, Australia, shanika.nanayakkara@sydney.edu.au.
authors.forename: Shanika
authors.initials: S
authors.lastname: Nanayakkara
authors.forename: S T M L D
authors.initials: ST
authors.lastname: Senevirathna
authors.forename: Nipuna B
authors.initials: NB
authors.lastname: Parahitiyawa
authors.forename: Tilak
authors.initials: T
authors.lastname: Abeysekera
authors.forename: Rohana
authors.initials: R
authors.lastname: Chandrajith
authors.forename: Neelakanthi
authors.initials: N
authors.lastname: Ratnatunga
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hitomi
authors.forename: Hatasu
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Kouji H
authors.initials: KH
authors.lastname: Harada
authors.forename: Akio
authors.initials: A
authors.lastname: Koizumi
mesh_terms: D016022:Case-Control Studies; D059472:Exome; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics / Q000378:metabolism; D013188:Sri Lanka / Q000453:epidemiology
chemical_list: C460019:KCNA10 protein, human; D007797:Laminin; D051637:Shaker Superfamily of Potassium Channels; C058783:laminin beta2