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04-03-2012 | Genetics | Article

Susceptibility to arsenic-induced skin lesions dependent on genotype


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MedWire News: A study carried out in Bangladeshi individuals reveals that genetics may explain why some people have a more extreme cutaneous reaction to arsenic exposure than others.

"Whatever the source of exposure, different individuals vary with respect to their susceptibility to the toxicity of arsenic," explained study author Habibul Ahsan (University of Chicago, Illinois, USA) in a press statement.

"Even if they consume or are exposed to arsenic at the same dose and duration, some individuals will manifest toxicity phenotypes and others won't."

Arsenic is a common drinking water contaminant in Bangladesh and has been linked to a variety of health problems, including skin cancer.

To assess whether genetics can predict an individual's response to arsenic exposure, Ahsan and team genotyped 1085 Bangladeshi individuals with arsenic-induced premalignant skin lesions and 1794 controls from the same region who had been exposed to arsenic but had no skin lesions for five single nucleotide polymorphisms (SNPs; rs9527, rs11191527, rs4919694, rs4290163, and rs11191659) in the AS3MT gene. AS3MT is thought to be involved in arsenic metabolism in the human body.

The five AS3MT SNPs were highlighted in a genome-wide association study including 300,000 SNPs carried out in a panel of 1313 arsenic-exposed Bangladeshi individuals. Ahsan and team found that of the five possible SNPs, rs9527 was significantly associated with arsenic-associated skin lesion risk. More specifically, carriers of the A allele of the rs9527 SNP had increased risk for skin lesions, as well as a reduced level of the arsenic metabolising enzyme dimethylarsinic acid (DMA).

The SNP rs11191659 also showed a trend for association with arsenic-induced skin lesions, but it was not statistically significant.

"This makes perfect sense," said Ahsan. "It gives us a very coherent story that we can now investigate in relation to other arsenic pathologies and in relation to a wide range of arsenic doses in this population."

He continued: "Now that we understand the molecular basis of some of this disease risk, it is conceivable to now think of incorporating this information into testing, evaluating, or potentially coming up with successful biomedical interventions.

"By exploiting these metabolic pathways for a subgroup of individuals who will really be at higher risk for getting those diseases, we may be able to reduce fatal outcomes in this population."

The results of this study are published in PLoS Genetics.

By Helen Albert

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