Increased level of organochlorine pesticides in chronic kidney disease patients of unknown etiology: role of GSTM1/GSTT1 polymorphism.
Chronic kidney disease (CKD) of unknown etiology represents about 16% of CKD patients in Indian subcontinents and 10% worldwide. The aetiology of CKD of unknown etiology remains unclear though epidemiological studies indicate the involvement of the environmental toxins. Organochlorine pesticides (OCPs) have been detected in general population in India. It is possible that polymorphism of xenobiotic metabolizing enzymes (XMEs) may play an important role in this process. In this we intend to find out blood levels of OCPs in CKD patients of unknown etiology and to evaluate the consequence of glutathione S-transferase (GST) gene polymorphism on the same. We have assessed 270 CKD patients and 270 age-sex-matched healthy controls for this study. The blood OCP levels were analyzed by gas chromatograph. GSTM1, GSTT1 genotyping were carried out by multiplex PCR. Blood levels of HCH, endosulfan and total pesticides were significantly higher in CKD patients and negatively correlated with eGFR. The combined frequency of GSTM1(-)/GSTT1(-) genotype increased the risk of CKD by 1.8-fold as compared to healthy controls. To find out the dependence of blood OCPs level on genotype, we carried out logistic regression analysis and results revealed that GSTM1(-)/GSTT1(-) genotype associated significantly with a number of OCPs namely γ-HCH, p,p'-DDT and total pesticides. Polymorphism of XMEs not only increased accumulation of pesticides but also aggravates kidney dysfunction as evident from significant decrease in eGFR.
Environmental Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G.T.B. Hospital, Dilshad Garden, Delhi 110095, India. Electronic address: manushisiddharth@gmail.com.
Manushi
M
Siddarth
Sudip K
SK
Datta
Md
M
Mustafa
Rafat S
RS
Ahmed
Basu D
BD
Banerjee
Om P
OP
Kalra
Ashok K
AK
Tripathi
D000328:Adult; D016022:Case-Control Studies; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood*; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010575:Pesticides / Q000097:blood*; D011110:Polymorphism, Genetic; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D012306:Risk
D004785:Environmental Pollutants; D005982:Glutathione Transferase; D006843:Hydrocarbons, Chlorinated; D010575:Pesticides; C413545:glutathione S-transferase T1
CKD; DDE; DDT; EDTA; GST; GSTs; HCH; OCPs; OS; XMEs; chronic kidney disease; dichlorodiphenyldichloroethylene; dichlorodiphenyltrichloroethane; eGFR; estimated glomerular filtration rate; ethylenediaminetetraacetic acid; glutathione S-transferase; hexachlorocyclohexane; organochlorine pesticides; oxidative stress; xenobiotic metabolizing enzymes