Int. J. Environ. Res. Public Health 2009, 6 1006 of the highest clinical interest is ALAD. When ALAD activity is deficient due to lead poisoning, erythrocyte synthesis become inhibited and blood hemoglobin concentrations become lower. In the second step of heme synthesis, ALAD catalyzes the formation of porphobilinogen from two molecules of ALA. ALAD is the most sensitive enzyme to lead in the heme pathway and has a high affinity for the metal. Lead binds the enzyme’s SH group, which normally binds zinc, preventing the binding of ALA [28]. Because lead effectively inhibits ALAD activity, resulting in accumulation of ALA in blood and urine, urinary ALA has also been used as a biomarker for lead exposure or a marker of early biologic effect of lead [28,29]. In this study, we did not find any significant differences for blood hemoglobin, hematocrit, red blood cell count, ZnPP, and serum and urinary ALA levels between GG, and GC genotype of ALAD. These may be explained by the fact that our study subjects were all adults, and who were only exposed to lead environmentally unlike chronically exposed lead workers, and the mean value of blood lead level in this study subject with ALAD carrier (GC genotype) was only 4.5 g/dL, which was lower than the minimum level for lead poisoning (<10 g/dL for children under 6, recommended by CDC [9]). So, these findings might be resulting from the low blood lead levels, which may not induce hemopoietic abnormalities and consequently not inhibit ALAD activity, effectively. Table 2. Biomarkers of lead exposure among non-occupationally lead exposed Japanese. Variable ALAD1 (GG) ALAD2 (GC) Blood lead level, μg/dL 3.2 + 0.19 4.4 + 0.58 sALA, ng/mL 9.1 + 0.39 10.2 + 0.91 uALA, mg/g creatinine 0.85 + 0.05 0.81 + 0.11 ZnPP, μM 19.0 + 0.54 21.2 + 1.0 Hb, mg/dL 14.3 + 1.6 14.7 + 1.7 All value are shown as mean + SD sALA: Serum 5-aminolevulinic acid, uALA: Urinary 5-aminolevulinic acid ZnPP: Zinc protoporphyrin, Hb: Hemoglobin P 0.02 0.28 0.70 0.05 0.37 4. Conclusions Acknowledgements This is the first descriptive report of the association between ALAD2 genotype and blood lead levels among non-occupationally lead exposed Japanese subjects, although there were some limitations such as lack of data for alcohol consumption and ALAD activity level. The present findings as well as lead toxicity complications will be examined in further longitudinal studies. We thank to Dr. Kazuyuki Omae and Mrs. Kanae Hosoda for their advice and technical support.