title: Possibilities of newer ALAD polymorphism influencing human susceptibility to effects of inorganic lead on the neurobehavioral functions.
abstract: OBJECTIVE
  A cross-sectional study was conducted to study the association between some new ALAD polymorphism and susceptibility to effects of inorganic lead on the neurobehavioral functions.
  
  
  METHODS
  We recruited 120 healthy male workers with lead exposure in a factory which manufacture lead stabilizer. The ALAD SNPs studied were HpyCH4, HpyIV RFLP in intron 6, Rsa and Msp RFLP in exon 4, Sau3A in intron 12 and Rsa39488 in exon 5. The World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) and a few other tests were used. General linear model (GLM) was applied to compare outcome scores between subgroups of each ALAD SNP while controlling for possible confounders.
  
  
  RESULTS
  The mean age of the workers was 39.7 years (S.D. 10.7), mean exposure duration of 10.2 years (S.D. 7.9) and mean blood lead of 22.1 microg/dl (S.D. 9.4). Among the 6 SNPs studied, Rsa and Rsa39488 appear to be the main candidate SNPs. Workers with Rsa and Rsa39488 ALAD 2-2 genotypes fare significantly better in the Aiming Pursue Test Correct (AC), Groove Peg Board non-preferred hand (GPNP), Groove Peg Board Mean (GPM), San Ana Preferred Hand (SAP), San Ana Both Hands (SAB) and AC, GPNH, GPM, Digit Symbol (DIS) tests; respectively compared to Rsa and Rsa39488 ALAD 1-1/1-2 genotypes adjusted for age, race, exposure duration and blood lead levels.
  
  
  CONCLUSIONS
  The presence of the homozygote Rsa and Rsa39488 ALAD 2-2 seems to offer some protection against the effect of lead on motor dexterity function. While it may appear that newer ALAD polymorphism other than the commonly reported Msp SNP might influence human susceptibility to effects of inorganic lead on the neurobehavioral functions further study involving a larger cohort of workers with Rsa and Rsa39488 ALAD2 allele would be needed to confirm this inference.
authors.affiliation: Department of Community, Occupational & Family Medicine, National University of Singapore, Singapore, Republic of Singapore. cofcse@nus.edu.sg
authors.forename: Sin-Eng
authors.initials: SE
authors.lastname: Chia
authors.forename: Zhou
authors.initials: Z
authors.lastname: Huijun
authors.forename: Tham Mei
authors.initials: TM
authors.lastname: Theng
authors.forename: Eric
authors.initials: E
authors.lastname: Yap
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D001519:Behavior / Q000187:drug effects*; D003430:Cross-Sectional Studies; D004391:Dust; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007854:Lead / Q000009:adverse effects* / Q000097:blood; D020265:Lead Poisoning, Nervous System, Adult / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000523:psychology; D008297:Male; D008669:Metallurgy; D008875:Middle Aged; D009048:Motor Skills / Q000187:drug effects; D009483:Neuropsychological Tests; D009784:Occupational Diseases / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000523:psychology; D016273:Occupational Exposure; D010087:Oxides / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D000623:Porphobilinogen Synthase / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012846:Singapore
chemical_list: D000393:Air Pollutants; D004391:Dust; D010087:Oxides; D007854:Lead; C047365:lead oxide; D000623:Porphobilinogen Synthase