US EPA

711011 

Journal Article 

Polymorphisms in the TNF-α and IL10 gene promoters and risk of arsenic-induced skin lesions and other nondermatological health effects 

Banerjee, N; Nandy, S; Kearns, JK; Bandyopadhyay, AK; Das, JK; Majumder, P; Basu, S; Banerjee, S; Sau, TJ; States, JC; Giri, AK 

2011 

1 

Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 

121 

1 

132-139 

English 

21357384 

10.1093/toxsci/kfr046 

WOS:000289807200013 

In West Bengal, India, at present more than 26 million people are exposed to arsenic through drinking water. Among them only 15%-20% manifest arsenic-induced non-cancerous, precancerous and cancerous skin lesions indicating that genetic variants play important role in arsenic susceptibility. Chronic arsenic exposure has been associated with impairment of immune systems in the exposed individuals. Because cytokines are important immune mediators, alteration in expression of these gene products may lead to arsenic-specific disease manifestations. The aim of the present work was to investigate the association between the TNF-α-308G>A (rs1800629) and IL10 -3575T>A (rs1800890) polymorphisms and arsenic-induced dermatological and non-dermatological health outcomes. A case-control study was conducted in West Bengal, India, involving 207 cases with arsenic-induced skin lesions and 190 controls without skin lesions having similar arsenic exposure. The polymorphisms were determined using conventional PCR-sequencing method. ELISA was done to determine the serum levels of the two cytokines TNF-α and IL10. Associations between the polymorphisms studied and non-dermatological health effects in the study subjects were determined from our epidemiological survey data. Individuals with GA/AA (-308TNF-α) and TA/AA (-3575IL10) genotypes were at higher risk of developing arsenic-induced skin lesions, ocular and respiratory diseases. Also the -308TNF A allele corresponded to a higher production of TNF-α and -3575IL10 A allele corresponded to a lower production of IL10. Thus the polymorphisms studied impart significant risk towards development of arsenic-induced dermatological and non-dermatological health effects in the chronically exposed population of West Bengal, India. 

arsenic; IL10; polymorphisms; skin lesions; susceptibility; TNF-alpha