Environmental Health and Preventive Medicine

, Volume 20, Issue 5, pp 354–359

Whole-exome sequencing reveals genetic variants associated with chronic kidney disease characterized by tubulointerstitial damages in North Central Region, Sri Lanka

  • Shanika Nanayakkara
  • STMLD Senevirathna
  • Nipuna B. Parahitiyawa
  • Tilak Abeysekera
  • Rohana Chandrajith
  • Neelakanthi Ratnatunga
  • Toshiaki Hitomi
  • Hatasu Kobayashi
  • Kouji H. Harada
  • Akio Koizumi
Regular Article

DOI: 10.1007/s12199-015-0475-1

Cite this article as:
Nanayakkara, S., Senevirathna, S., Parahitiyawa, N.B. et al. Environ Health Prev Med (2015) 20: 354. doi:10.1007/s12199-015-0475-1

Abstract

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. 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.

Conclusion

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.

Keywords

Chronic kidney disease Sri Lanka KCNA10 LAMB2 Genetic susceptibility 

Funding information

Funder NameGrant NumberFunding Note
Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology in Japan

    Copyright information

    © The Japanese Society for Hygiene 2015

    Authors and Affiliations

    • Shanika Nanayakkara
      • 1
    • STMLD Senevirathna
      • 2
    • Nipuna B. Parahitiyawa
      • 3
    • Tilak Abeysekera
      • 4
    • Rohana Chandrajith
      • 5
    • Neelakanthi Ratnatunga
      • 6
    • Toshiaki Hitomi
      • 7
    • Hatasu Kobayashi
      • 7
    • Kouji H. Harada
      • 7
    • Akio Koizumi
      • 7
    1. 1.Institute of Dental Research, Faculty of DentistryUniversity of SydneySydneyAustralia
    2. 2.School of Computing, Engineering and MathematicsUniversity of Western SydneySydneyAustralia
    3. 3.School of Pathology and Laboratory MedicineThe University of Western AustraliaPerthAustralia
    4. 4.Department of Pharmacology, Faculty of MedicineUniversity of PeradeniyaPeradeniyaSri Lanka
    5. 5.Department of Geology, Faculty of ScienceUniversity of PeradeniyaPeradeniyaSri Lanka
    6. 6.Department of Pathology, Faculty of MedicineUniversity of PeradeniyaPeradeniyaSri Lanka
    7. 7.Department of Health and Environmental Sciences, Graduate School of MedicineKyoto UniversityKyotoJapan

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