Polymorphisms in the TNF-a and IL10 Gene Promoters and Risk of Arsenic-Induced Skin Lesions and Other Nondermatological Health Effects

Banerjee, Nilanjana and Nandi, Sanjay and Kearns, James K and Bandyopadhyay, Apurba and Das, Jayanta K and Majumder, Papiya and Basu, Santanu and Banerjee, Saptarshi and Sau, Tanmoy Jyoti and States, J. Christopher and Giri, Ashok K (2011) Polymorphisms in the TNF-a and IL10 Gene Promoters and Risk of Arsenic-Induced Skin Lesions and Other Nondermatological Health Effects. Toxicological Science, 121 (1). pp. 132-139.

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    Abstract

    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 noncancerous, 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-a 2308G>A (rs1800629) and IL10 23575T>A (rs1800890) polymorphisms and arsenic-induced dermatological and nondermatological 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 tumor necrosis factor a (TNF-a) and interleukin 10 (IL10). Associations between the polymorphisms studied and nondermatological health effects in the study subjects were determined from our epidemiological survey data. Individuals with GA/AA (2308 TNF-a) and TA/AA (23575 IL10) genotypes were at higher risk of developing arsenic-induced skin lesions, ocular, and respiratory diseases. Also the 2308 TNF A allele corresponded to a higher production of TNF-a, and 23575 IL10 A allele corresponded to a lower production of IL10. Thus, the polymorphisms studied impart significant risk toward development of arsenic-induced dermatological and nondermatological health effects in the chronically exposed population ofWest Bengal, India.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/1193
    Subjects: Molecular & Human Genetics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Mr Shyamal Nath
    Date Deposited: 30 Dec 2011 13:20
    Last Modified: 11 Jan 2013 12:08
    Official URL: http://dx.doi.org/10.1093/toxsci/kfr046
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