Haplotypes of vitamin D receptor modulate the circulating levels of lead in exposed subjects

• Published in: Archives of toxicology Vol. 82; no. 1; pp. 29 - 36
• Main Authors: Rezende, Vania B., Barbosa, Fernando, Montenegro, Marcelo F., Sandrim, Valeria C., Gerlach, Raquel F., Tanus-Santos, Jose E.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.01.2008; Springer; Springer Nature B.V
• Subjects: Adult; Alleles; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Chemical and industrial products toxicology. Toxic occupational diseases; Deoxyribonucleases, Type II Site-Specific - genetics; Environmental Exposure; Environmental Health; Female; Freeze Drying; Genotype; Haplotypes; Humans; Inorganic Compounds; Lead - blood; Male; Mass Spectrometry; Medical sciences; Metals and various inorganic compounds; Occupational Medicine/Industrial Medicine; Pharmacology/Toxicology; Polymorphism, Single Nucleotide - genetics; Receptors, Calcitriol - genetics; Reverse Transcriptase Polymerase Chain Reaction; Spectrophotometry, Atomic; Toxicology; Vitamin D; Plasma lead; Whole blood lead; Haplotype; Toxicogenetics; Vitamin D receptor; Polymorphism; Human; Genetic variability; Genotype; Heavy metal; Blood plasma; Whole blood; Vitamin D; Lead; Biological receptor
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-007-0231-4

Genetic factors influence whole blood lead (Pb-B) concentrations in lead exposed subjects. This study aimed at examining the combined effects (haplotype analysis) of three polymorphisms ( BsmI , ApaI and FokI ) in vitamin D receptor (VDR) gene on Pb-B and on the concentrations of lead in plasma (Pb-P), which is more relevant to lead toxicity, in 150 environmentally exposed subjects. Genotypes were determined by RFLP, and Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. Subjects with the bb ( BsmI polymorphism) or ff ( FokI polymorphism) genotypes have lower B-Pb than subjects in the other genotype groups. Subjects with the aa ( ApaI polymorphism) or ff genotypes have lower P-Pb than subjects in the other genotype groups. Lower Pb-P, Pb-B, and %Pb-P/Pb-B levels were found in subjects with the haplotype combining the a, b, and f alleles for the ApaI , BsmI , and FokI polymorphisms, respectively, compared with the other haplotype groups, thus suggesting that VDR haplotypes modulate the circulating levels of lead in exposed subjects.