title: [Genetic polymorphism and susceptibility to occupational chronic manganism: a case-control study].
abstract: OBJECTIVE
  In a case-control study, the possible genetic factors relevance to occupational chronic manganism were investigated.
  
  
  METHODS
  Forty-nine manganisms who were welders and ferromanganese smelters occupationally exposed to manganese dust and fume from three metallurgical industries, and fifty unrelated healthy control subjects who were working same workshops were recruited. The subjects were matched for sex, age, cigarette and alcohol intake. The manganese exposure duration was also matched in this case-control study. Genetic polymorphism of cytochrome P450 2D6L (CYP2D6L) gene and NAD(P)H: quinone oxidreductase (NQO1) genes from all subjects were investigated. The mutations of CYP2D6L gene located exon 6 were analyzed by a polymerase chain reaction (PCR)-based DNA amplification combined with Hha I restriction fragment length polymorphism (RFLP). The substitution of 609(C-T) at exon 6 of DT-diaphroase gene was analyzed by PCR combined Hinf I RFLP.
  
  
  RESULTS
  The frequency of polymorphic allels, a mutation of CYP2D6, was significantly lower in patients with manganism (16.3%) than that of the controls (29.0%). A significant association was also found between the homozygote variant of CYP2D6L gene and occupational manganism. These results suggest that the CYP2D6 gene might be one of the susceptibility genes for Mn-induced neurotoxicity. The allele and genotype frequencies of NQO1 gene were similar in the manganism cases and control subjects.
  
  
  CONCLUSIONS
  It is possible that CYP2D6 gene may be a valuable susceptibility biomarker responded to Mn-induced central nervous system disorders in workers exposed to manganese.
authors.affiliation: Institute of Occupational Medicine, Chinese Academy of Preventive Medicine, Beijing 100050.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.forename: F
authors.initials: F
authors.lastname: He
authors.forename: P
authors.initials: P
authors.lastname: Chan
authors.forename: Z
authors.initials: Z
authors.lastname: Pan
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: X
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002908:Chronic Disease; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020149:Manganese Poisoning / Q000235:genetics*; D009154:Mutation; D009784:Occupational Diseases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D019389:Cytochrome P-450 CYP2D6