연작업자들에서의 δ -aminolevulinic acid dehydratase 유전형질의 다형성이 신기능에 미치는 영향 = Influence of δ-aminolevulinic Acid Dehydratase Polymorphism on Renal Function in Lead Workers

다국어 초록 (Multilingual Abstract)

δ-aminolevulinic acid hehydratase (ALAD) is a polymorphic enzyme that has two alleles, ALAD1 (ALAD1-1 as phenotype) and ALAD2 (ALAD1-2 or ALAD2-2 as phenotype). ALAD genotype has been reported to modify the toxicokinetics of lead. To investigate the influence of ALAD genotype polymorphism on renal function in lead workers, author studied 1022 male lead workers and 149 non lead workers in the same industries. For the cross-sectional renal function indices, blood urea nitrogen (BUN), serum creatinine, uric acid and total protein were selected. Blood lead and blood zinc protoporphyrin were also measured as indices of lead exposure. Information on weight, age, job duration, smoking & drinking history were collected.
Following results are as follows:
1. Whereas the mean (standard deviation) of blood lead and blood ZPP of lead workers were 27.2±12.5 ㎍/㎗ and 57.7±37.8 ㎍/㎗, those of non-lead workers in the same premises were 14.9±6.5 ㎍/㎗ and 44.6± 15.8 ㎍/㎗ respectively. The difference of mean blood lead and blood ZPP between two groups were statistically significant.
2. Whereas the prevalence of the variant allele, ALAD2 in 1022 lead workers was 10.2 %, the prevalence of that in 149 non-lead workers was 7.4 %. But there was no difference of prevalence between two groups.
3. The mean±standard deviation of blood lead of subjects with ALAD1 was 25.5± 12.7 ㎍/㎗ and was slightly lower than that of subjects with ALAD2 (26.5±10.9 ㎍/㎗), and the mean±standard deviation of blood ZPP of subjects with ALAD1 was slightly higher than that of subjects with ALAD2 (56.7±37.3 ㎍/㎗ vs 48.9±18.6 ㎍/㎗). But the differences of blood lead and blood ZPP between two genotypes were not statistically significant.
4. There were no differences of cross-sectional renal function indices (BUN, serum creatinine, uric acid and total protein) either by lead workers and non-lead workers or two genotypes.
5. In multiple regression analysis of ALAD genotype on BUN after controlling for possible confounders (sex, weight, job duration, smoking and drinking status), the mean of BUN in ALAD2 subjects was 0.629 ㎎/㎗ lower than ALAD1 subjects with a weak statistical significance (p=0.07). But in logistic analysis of ALAD genotype on median value of BUN revcaled that subjects of ALAD2 genotype were 32% less likely to have median value or more of BUN than subjects of ALAD1 with odd ratio of 0.618 (95% confidence interval 0.411-0.920).
6. In multiple regression analysis of ALAD genotype on serum creatinine after controlling for possible confounders (sex, weight, job duration, smoking and drinking status), the mean of serum creatinine in ALAD2 subjects was 0.0271 ㎎/㎗ lower than ALAD1 subjects with statistical significance (p=0.02). On the other hand, in logistic analysis of ALAD genotype on median value of serum creatinine revealed that subjects of ALAD2 genotype were 30% less likely to have median value or more of scrum creatinine than subjects of ALAD1 with odd ratio of 0.700 (95% confidence interval 0.442-1.080).
With the above results, it was found that the variant allcle, ALAD2 appeared to modify the association of lead and renal function and ALAD2 genotype may be supportive for the protective effect of lead.