Increased level of organochlorine pesticides in chronic kidney disease patients of unknown etiology: Role of GSTM1/GSTT1 polymorphism

• Published in: Chemosphere (Oxford) 2014-02, Vol.96, p.174-179
• Main Authors: Siddarth, Manushi, Datta, Sudip K., Mustafa, MD, Ahmed, Rafat S., Banerjee, Basu D., Kalra, Om P., Tripathi, Ashok K.
• Format: Article
• Language: English
• Subjects: Adult; Air. Soil. Water. Waste. Feeding; Biological and medical sciences; Case-Control Studies; eGFR; Environment. Living conditions; Environmental Exposure - statistics & numerical data; Environmental Pollutants - blood; Female; Genotype; Glutathione Transferase - metabolism; GSTs; HCH; Humans; Hydrocarbons, Chlorinated - blood; India - epidemiology; Male; Medical sciences; Middle Aged; OCPs; Pesticides - blood; Pesticides, fertilizers and other agrochemicals toxicology; Polymorphism, Genetic; Public health. Hygiene; Public health. Hygiene-occupational medicine; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - epidemiology; Renal Insufficiency, Chronic - genetics; Risk; Toxicology
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2013.10.029

•Presence of OCPs in CKD patients of unknown etiology.•Polymorphism of GSTs gene significantly associated with OCPs in CKD.•Polymorphism of GSTs and accumulation of pesticides aggravates kidney dysfunction.•First report of its kind on Indian population. 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.