An Integrative Study of the Genetic, Social and Environmental Determinants of Chronic Kidney Disease Characterized by Tubulointerstitial Damages in the North Central Region of Sri Lanka
Open Access
- 1 January 2014
- journal article
- Published by Oxford University Press (OUP) in Journal of Occupational Health
- Vol. 56 (1), 28-38
- https://doi.org/10.1539/joh.13-0172-oa
Abstract
Objectives: Previous investigations on chronic kidney disease of unknown etiology characterized by tubulointerstitial damages (CKDu) in the North Central Region (NCR) of Sri Lanka have supported the involvement of social, environmental and genetic factors in its pathogenesis. Methods: We conducted a social-environmental-and-genetic epidemiology study on a male population in NCR to investigate the genetic and environmental contributors. We recruited 311 case-series patients and 504 control candidates. Of the 504 control candidates, 218 (43%) were eliminated because of the presence of hypertension, proteinuria, high HbA1c, high serum creatinine or high alpha-1 microglobulin in urine. Results and Discussion: None of 18 metals measured (μg//) in urine, including Cd, As and Pb, showed significantly higher concentrations in cases compared with controls. As speciation results showed that 75–80% of total urinary As was in the form of arsenobetaine, which is non-toxic to humans. None of the metal concentrations in drinking water samples exceeded guideline values. A genome-wide association study (GWAS) was conducted to determine the genetic contributors. The GWAS yielded a genome-wide significant association with CKDu for a single nucleotide polymorphism (SNP; rs6066043; p=5.23 × 10−9 in quantitative trait locus analysis; p=3.73 × 10−9 in dichotomous analysis) in SLC13A3 (sodium-dependent dicarboxylate transporter member 3). The population attributable fraction and odds ratio for this SNP were 50% and 2.13. Genetic susceptibility was identified as the major risk factor for CKDu. However, 43% of the apparently healthy malepopulation suffers from non-communicable diseases, suggesting their possible influence on CKDu progression.(J Occup Health 2014; 56: 28–38)Keywords
This publication has 32 references indexed in Scilit:
- Variants on Chromosome 6p22.3 Associated With Blood Pressure in the HyperGEN Study: Follow-Up of FBPP Quantitative Trait LociAmerican Journal of Hypertension, 2011
- Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri LankaEnvironmental Health and Preventive Medicine, 2011
- Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: a cohort study in Medawachchiya, Sri LankaEnvironmental Health and Preventive Medicine, 2011
- Evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: a cross-sectional studyEnvironmental Health and Preventive Medicine, 2011
- The need for robust validation for MDRD-based glomerular filtration rate estimation in various CKD populationsNephrology Dialysis Transplantation, 2011
- Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: geographic distribution and environmental implicationsEnvironmental Geochemistry and Health, 2010
- Urinary Arsenic Species and CKD in a Taiwanese Population: A Case-Control StudyAmerican Journal of Kidney Diseases, 2009
- Revised Equations for Estimated GFR From Serum Creatinine in JapanAmerican Journal of Kidney Diseases, 2009
- Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1Genomics, 2008
- Reduction in Urinary Arsenic Levels in Response to Arsenic Mitigation Efforts in Araihazar, BangladeshEnvironmental Health Perspectives, 2007