[Genetic polymorphisms of MPO, NQO1, GSTP1, UGT1A6 associated with susceptibility of chronic benzene poisoning].
OBJECTIVE
To explore the relationship between genetic polymorphisms in MPO, NQO1, GSTP1, UGT1A6 and susceptibility to chronic benzene poisoning (BP).


METHODS
A case-control study was conducted. 268 BP patients and 268 workers occupationally exposed to benzene without poisoning manifestations were investigated. The genotype of MPO (rs7208693), NQO1 (rs1800566), GSTP1 ( rs947894 ) and UGT1A6 (rs6759892, rs1105879, rs4124874 ,rs3755319 ,rs887829 and rs4148323) were tested by the TaqMan PCR method.


RESULTS
There was a 0.675-fold (95% CI 0.434 - 0.994, P = 0.046) decreased risk of BP in the subjects with GSTP1 rs947894 G alleles compared with those carrying AA genotype. In the subjects carrying allele of MPO rs7208693 A, the risk of BP increased for the individuals carrying allele of UGT1A6 rs6759892 G (OR = 2.702, P = 0.024) compared to those with TT genotype or the individusals carrying allel of UGT1A6 rs1105879 C (OR = 2.619, P = 0.035) compared to those with TT genotype. In drinking population, the individuals carrying the NQO1 rs1800566 TT homozygote genotype had a 9.000-fold (5% CI 1.460 - 55.478, P = 0.021) risk of BP compared to those with CT + CC genotypes. In smoking population, there was 7.000-fold (95% CI 1.555 - 31.575, P = 0.012) of risk in BP subjects carrying NQO1 rs1800566T/T genotype, compared with those carrying CC + CT genotype. Haplotyes analysis of polymorphisms in UGT1A6 showed that compared with those carrying TAATGG haplotype, there was a 1.446-fold (OR = 1.446, 95% CI 1.005 - 2.080, P = 0.046) increased risk of BP for those carrying TACGGG haplotype.


CONCLUSIONS
The subjects carrying allele of MPO rs7208693 A and UGT1A6 rs6759892 G or rs1105879 C at the same time could be more susceptible to BP. The subjects carrying NQO1 rs1800566 TT genotype and together with the habit of smoking or drinking could be more susceptible to BP. Those subjects carrying TAATGG haplotype of UGT1A6 could increase the risk of BP. Further studies should be needed on the association between the genetic polymorphisms in GSTP1 and the risk of BP.
Sun
Pin
P
Department of Occupational Health, School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai 200032, China. 041102088@fudan.edu.cn
Zhang
Zhongbin
Z
Wan
Junxiang
J
Shao
Minhua
M
D000328:Adult; D000483:Alleles; D001554:Benzene / Q000506:poisoning*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009784:Occupational Diseases / Q000235:genetics; D016273:Occupational Exposure; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D055815:Young Adult
D009195:Peroxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D001554:Benzene