Associations of ALAD Genotype with Renal Function Indices in Lead Workers

Lee, Sung Soo; Kim, Jin Ho; Kim, Nam Soo; Kim, Hwa Sung; Ahn, Kyu Dong; Lee, Byung Kook

Abstract

OBJECTIVES
delta-Aminolevulinic acid dehydratase (ALAD) is a polymorphic enzyme that has two alleles, ALAD1 (ALAD1-1 as genotype) and ALAD2 (ALAD1-2 or ALAD2-2 as genotype). ALAD genotype has been reported to modify the pharmacokinetics and toxicity of lead. The authors investigated the influence of ALAD genotype polymorphism on renal function in lead workers
METHODS
We studied 935 male lead workers and 87 male non-lead workers in the same industries. For cross-sectional renal indices, blood urea nitrogen (BUN), serum creatinine, serum uric acid and urine total protein were selected. Blood lead level was also measured an index of lead exposure. Information on weight, age, job duration, and smoking and drinking habits was collected.
RESULTS
Whereas the mean blood lead level of lead workers was 25.4+/-10.9 microgram/dL, that of non-lead workers in the same premise was 10.1+/-2.8 microgram/dL, and the difference between the two groups was statistically significant. Whereas the prevalence of the variant allele, ALAD2 in 935 lead workers was 10.6%, that in 87 non-lead workers was 4.6%. However there was no difference of prevalence between the two groups. The mean blood lead level of subjects with ALAD1 was 23.9+/-11.4 microgram/dL, which was slightly lower than that of subjects with ALAD2 (25.8+/-10.7 microgram/dL). However, this difference was not statistically significant. After adjustment for the covariates, the subjects with ALAD2 allele were 12.8% less likely to have a median value or more of BUN than subject with ALAD1. The adjusted odds ratio was 0.59 (95% confidence interval; 0.38-0.91). After adjustment for the covariates, the subjects with ALAD2 allele were 9.3% less likely to have a median value or more of serum creatinine than subject with ALAD1. The adjusted odds ratio was 0.64 (95% confidence interval; 0.41-0.98).
CONCLUSIONS
From the above results, it was found that the variant allele, ALAD2 appeared to modify the association of lead and renal function, and that ALAD2 genotype may be supportive for the protective effect of lead.