The Effect of ALAD and VDR Polymorphism on the Hematopoietic Biomarkers in Lead Exposed Workers

Lee, Sung Soo; Kim, Nam Soo; Kim, Jin Ho; Kim, Yong Bae; Hwangbo, Young; Kim, Hwa Sung; Ahn, Kyu Dong; Lee, Byung Kook

Abstract

OBJECTIVES
This study was conducted with new workers who entered lead industries from 1992 to 2001 to evaluate the genetic susceptibility of ALAD (delta-aminolevulinic acid dehydratase) and VDR (vitamin D receptor) gene on health effect of lead exposure.
METHODS
Among the subjects of the database of lead industries at the Soonchunhyang University Institute of Industrial Medicine, only new workers were selected for this study. The total of eligible workers for this category was 3,540 workers, including non lead exposed workers of same lead industries. From stored blood in specimen bank of Soonchunhyang University, genotype of ALAD and VDR were measured using PCR method. Variables for this study were blood lead as an index of lead exposure, ZPP (zinc protoporphyrin in blood), urine ALA (delta-aminolevulinic acid), and hemoglobin as an index of hematopoietic effect of lead. Information on sex, job duration, and weight were collected for personal information. The data were analyzed using SAS (version 8.2) with descriptive analysis of t-test and multiple regression analysis.
RESULTS
Among 3,540 new employed study subjects during period of 1992-2001, 3,204 workers (90.5%) had ALAD genotype 1-1, while 336 workers (9.5%) had variant type of ALAD (1-2 or 2-2). For VDR genotype, 2,903 workers (89.7%) out of total tested 3,238 workers were belonged to type bb and 335 workers (10.5%) were type bB or BB. The distribution of genotype of ALAD and VDR were not different according to the job duration in male workers, but were different in female workers. The effect of ALAD and VDR genotype on blood lead were positively significant in the analysis of all cumulative data of new employed workers for 10 years. The effect of VDR genotype on blood lead were stronger than that of ALAD. While the variant ALAD gene made decrease of mean ZPP and ALA in urine after controlling for blood lead and other covariate, the variant VDR gene made increased the mean ZPP and ALA in urine in all cumulative data analysis and cross sectional analysis by job duration. For hemoglobin, ALAD and VDR genotype did not affect the mean value.
CONCLUSIONS
From the above our results, we found that ALAD and VDR genotype exerted significant effect in various way. We confirmed that the finding of a cross sectional study of protective effect of variant ALAD on the effect of blood lead on blood ZPP in our retrospective study design. It was found that VDR did not exert protective effect for lead exposure as the variant ALAD did.