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The aim of this study was to investigate the effect of G177C d-aminolevulinic acid dehydratase (ALAD) polymorphism (rs1800435) on the renal toxicity of lead, and the potential gene - environment interactions.
Methods
A cross-sectional survey was conducted within the cohort of ex-employees of a foundry situated in the north of France. This company ceased its activities in early 2003. Participation included the completion of a questionnaire and realization of blood (determination of lead, urea, creatinine and ALAD G177C polymorphism) and urinary samples (cadmium, retinol-binding-protein (RBP), N-acétyl-glucosaminidase (NAG) and its isoenzymes A and B). Four markers of renal function (urea and serum creatinine, creatinine clearance and estimated glomerular filtration rate) and 4 markers of proximal tubular dysfunction (RBP, NAG-A,-B and-T) were studied. Multiple regression models with interaction term were used.
Results
204 men and 4 women gave their consent to participate in this study. They were 32 to 66 years old at the time of inclusion (median 53 years). The cumulative duration of lead exposure ranged from 4 to 44 years (median 26 years), the cumulative blood lead index from 516 to 29736 µg/L x years (median 11809). The frequency of ALAD-2 allele was 9.4%. 35 subjects were heterozygotes (ALAD 1-2) and 2 homozygotes (ALAD 2-2). There were no significant differences for parameters assessing exposure to lead by genotype (ALAD 1-1 vs ALAD 1-2 or 2-2). ALAD-2 allele carriers showed a trend towards an increase in blood urea with blood lead levels at the date of the study (p = 0.06) and an increased urinary RBP with duration of lead exposure (p <0.01) and cumulative exposure index (p = 0.06).
Discussion
These results are broadly consistent with those of the literature and reinforce the idea that the nephrotoxicity of lead may be influenced by G177C ALAD polymorphisms.