title: Arsenic-related skin lesions and glutathione S-transferase P1 A1578G (Ile105Val) polymorphism in two ethnic clans exposed to indoor combustion of high arsenic coal in one village.
abstract: OBJECTIVE
  A total of 2402 patients with arsenic-related skin lesions, such as hyperkeratosis, hyperpigmentation or hypopigmentation, or even skin cancer in a few villages in Southwest Guizhou Autonomous Prefecture, China represent a unique case of endemic arsenism related with indoor combustion of high arsenic coal. This study aimed to investigate the cluster of arsenism cases and the possible relevant factors including GSTP1 polymorphism in two clans of different ethnic origin living in one village for generations.
  
  
  METHODS
  A questionnaire-based study was performed in 170 Miao clan P members, 10 of whom had arsenic-related skin diseases, and 153 Han clan G1 members, 50 of whom had arsenic-related skin diseases. The data were checked against the registration archives since the 1980s. At the same time, arsenic concentrations in samples of coal, indoor air, drinking water, corn and chilli pepper that were once baked over the stoves for desiccation, as well as in samples of urine and hair of clan members were determined. Glutathione S-transferase P1 (GSTP1) A1578G polymorphism was genotyped by a restriction fragment length polymorphism-based procedure.
  
  
  RESULTS
  Arsenism morbidity in Miao clan P was significantly lower than in the neighbouring Han clan G1 [5.9 vs. 32.7%, odds ratio (OR)=0.13, 95% confidence interval (CI): 0.06-0.27, P<0.0001]. No sex differences were confirmed inside both clans. Analyses of the environmental samples indicated that Miao clan P members were exposed to higher amounts of arsenic via inhalation and food ingestion. Hair and urine samples also proved a higher arsenic body burden in ethnic Miao individuals. No corresponding differences by sex were found. Higher frequencies of combined mutant genotype G/G1578 and A/G1578 (OR=4.72, 95% CI: 2.34-9.54, P<0.0001) and of mutant allele G1578 (OR=3.22, 95% CI: 2.00-5.18, P<0.0001) were detected in diagnosed arsenism patients than in non-diseased individuals. The Miao individuals showed a lower percentage of combined mutant genotypes (30.6 vs. 52.7%, OR=0.40, 95% CI: 0.19-0.84, P=0.015) as well as of mutant allele G1578 (OR=0.46, 95% CI: 0.24-0.88, P=0.017) than their Han neighbours.
  
  
  CONCLUSIONS
  Genetic predisposition influences dermal arsenism toxicity. The GSTP1 A1578G (Ile105Val) status might be a susceptibility factor for arsenic-related skin lesions.
authors.affiliation: Laboratory of Toxicology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Lin
authors.forename: Hui
authors.initials: H
authors.lastname: Du
authors.forename: Ji-Gang
authors.initials: JG
authors.lastname: Chen
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: Lu
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Meng
authors.forename: Tian-Bao
authors.initials: TB
authors.lastname: Zhang
authors.forename: Xin-Jiang
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Da-Ru
authors.initials: DR
authors.lastname: Lu
authors.forename: Klaus
authors.initials: K
authors.lastname: Golka
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D000328:Adult; D016902:Air Pollution, Indoor / Q000009:adverse effects / Q000032:analysis; D019943:Amino Acid Substitution; D001151:Arsenic / Q000032:analysis; D020261:Arsenic Poisoning / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D003031:Coal / Q000009:adverse effects; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005506:Food Contamination / Q000032:analysis; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012871:Skin Diseases / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*
chemical_list: D003031:Coal; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D001151:Arsenic