Abstract
A study on ALAD (G177C and T168C) and MGP (T-138C) gene polymorphisms associated with lead exposure in subjects from Saudi Arabia
Highlights
Delta aminolevulinic acid dehydratase (ALAD) gene polymorphisms and Matrix Gla (g-carboxyglutamic acid) protein T-138C polymorphisms were reported to affect the response of individuals to lead toxicity symptoms
It is important to note that the gene coding for ALAD enzyme is polymorphic in nature; the ALADG177C polymorphism yields two co-dominant alleles, ALAD-1 and ALAD-2 which have been implicated in susceptibility to lead toxicity
Studies have suggested that carriers of the ALAD2 allele have higher Blood lead levels (BLL) than ALAD1 subjects and are more susceptible to lead toxicity (Wetmur et al, 1991b; Kelada et al, 2001; Onalaja and Claudio, 2000; ATSDR, 2006)
Summary
Delta aminolevulinic acid dehydratase (ALAD) gene polymorphisms (rs1139488 – MspI and RsaI in exon 4) and Matrix Gla (g-carboxyglutamic acid) protein T-138C polymorphisms were reported to affect the response of individuals to lead toxicity symptoms. Lead displaces a zinc ion at the metal binding site (not the active site) producing inhibition through a change in the enzyme’s quaternary structure This inhibition of ALAD results in the buildup of aminolevulinic acid, detectable in the plasma and urine at BLL less than 10 μg/dl (Schwartz et al, 1995). MGP contains a fourth exon of unknown function that codes for 11 residues and lies between the transmembrane signal peptide and the putative recognition site for the gamma-carboxylase (Price et al, 2002; Afshin et al, 2001) This four-exon organization is essentially identical to that of bone Gla protein (112260), but is quite different from the two-exon organization encoding this region in other known vitamin K-dependent proteins. The T-138C polymorphism in MGP promoter region is known to either enhance or decrease synthesis of this protein, affecting the mineralization
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