RGD Reference Report - Polymorphisms in the TNF-alpha and IL10 gene promoters and risk of arsenic-induced skin lesions and other nondermatological health effects. - Rat Genome Database

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

Authors: Banerjee, N  Nandy, S  Kearns, JK  Bandyopadhyay, AK  Das, JK  Majumder, P  Basu, S  Banerjee, S  Sau, TJ  States, JC  Giri, AK 
Citation: Banerjee N, etal., Toxicol Sci. 2011 May;121(1):132-9. doi: 10.1093/toxsci/kfr046. Epub 2011 Feb 25.
RGD ID: 7364846
Pubmed: PMID:21357384   (View Abstract at PubMed)
PMCID: PMC3115675   (View Article at PubMed Central)
DOI: DOI:10.1093/toxsci/kfr046   (Journal Full-text)

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-alpha-308G>A (rs1800629) and IL10 -3575T>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 alpha (TNF-alpha) 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 (-308 TNF-alpha) and TA/AA (-3575 IL10) genotypes were at higher risk of developing arsenic-induced skin lesions, ocular, and respiratory diseases. Also the -308 TNF A allele corresponded to a higher production of TNF-alpha, and -3575 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 of West Bengal, India.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
skin disease severityIEP 7364846; 7364846associated with Arsenic PoisoningRGD 
skin disease susceptibilityIAGP 7364846associated with Arsenic Poisoning more ...RGD 
skin disease severityISOIL10 (Homo sapiens)7364846; 7364846associated with Arsenic PoisoningRGD 
skin disease  ISOIL10 (Homo sapiens)7364846; 7364846associated with Arsenic Poisoning more ...RGD 
skin disease susceptibilityISOIL10 (Homo sapiens)7364846; 7364846associated with Arsenic Poisoning and DNA:SNP:promoter:���3575T>A (human)RGD 
skin disease susceptibilityIAGP 7364846associated with Arsenic Poisoning and DNA:SNP:promoter:-308G>A (human)RGD 
skin disease severityISOTNF (Homo sapiens)7364846; 7364846associated with Arsenic PoisoningRGD 
skin disease susceptibilityISOTNF (Homo sapiens)7364846; 7364846associated with Arsenic Poisoning and DNA:SNP:promoter:-308G>A (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Abnormal skin morphology no_associationIAGP 7364846associated with Diabetes Mellitus more ...RGD 
Abnormal skin morphology susceptibilityIAGP 7364846associated with Diabetes Mellitus more ...RGD 
Abnormal skin morphology susceptibilityIAGP 7364846associated with Arsenic Poisoning and DNA:SNP:promoter:���3575T>ARGD 
Abnormal skin morphology susceptibilityIAGP 7364846associated with Arsenic Poisoning and DNA:SNP:promoter:-308G>ARGD 
Objects Annotated

Genes (Rattus norvegicus)
Il10  (interleukin 10)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Il10  (interleukin 10)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
AGER  (advanced glycosylation end-product specific receptor)
IL10  (interleukin 10)
TNF  (tumor necrosis factor)


Additional Information