Association of glycophorin A mutant frequency and urinary PAH metabolites influenced by genetic polymorphisms of GSTM1 in incineration workers

소각장 근로자에서 GSTM1의 유전자 다형성이 glycophorin A변이 발현율과 소변내 PAH 대사산물 농도와의 관계에 미치는 영향

Eighty-one workers including 38 employees directly incinerating industry wastes were recruited from a company located in South Korea. To evaluate the association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as internal dose of polycyclic aromatic hydrocarbon (PAH) exposure, and glycophorin A (GPA) mutation frequency, as an early biologic effect indicator. Urinary 1-OHPG levels were measured by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11. Erythrocyte GPA variant frequency (NN or NO) was assessed in MN heterozygotes with a flow cytometic assay. The GSTM1 and GSTT1 genotypes were assessed by a multiplex PCR method. The GPA NN phenotype frequency was higher in occupationally exposed group (n=14, mean$\pm$S.D. 6.6$\pm$12.0 in 10/SUP 6/ erythrocyte cells) than in non-exposed group (n=22, 2.1$\pm$3.5). Similarly, the GPA(NO or NN) phenotype frequency was higher in exposed group (n=14, 9.7$\pm$17.3) than non-exposed group (n=22, 4.2$\pm$6.3). The above differences failed to reach statistical significance, but a significant increase was seen in GPA variant frequency levels with increase in urinary 1-OHPG levels (Spearman's correlation: p=0.06 (NO), p=0.07 (NO or NN)). When this association was evaluated by GSTM1 genotype status, the association between GPA mutation and urinary 1-OHPG levels was stronger in individuals with GSTM1 present genotype (Spearmans correlation; r=0.50, p=0.02). These results suggest that the association between urinary 1-OHPG and GPA mutation is be modulated by the GSTM1 genotype.