title: Polymorphism in Cytochrome P450 2D6, Glutathione S-Transferases Pi 1 Genes, and Organochlorine Pesticides in Alzheimer Disease: A Case-Control Study in North Indian Population.
abstract: OBJECTIVE
  It has been assumed that the association between Alzheimer disease (AD) and pesticides may be stronger among genetically susceptible individuals. The aim of the study was to examine the genetic polymorphism in cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1) with respect to organochlorine pesticides (OCPs) and metals in AD.
  
  
  METHODS
  This study included 100 patients with AD and 100 age-matched controls. The genetic polymorphisms were analyzed by restriction fragment length polymorphism. The OCPs and serum metal levels were determined using gas chromatography and an autoanalyzer, respectively.
  
  
  RESULTS
  We found a statistically significant association between AD and high levels of β-hexachlorocyclohexane (β-HCH; odds ratio [OR] = 2.064, 95% confidence intervals [95% CIs] = 1.373-3.102, dieldrin [OR = 2.086, 95% CI = 1.224-3.555], and copper [OR = 1.038, 95% CI = 1.012-1.064). The significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even appears to have a protective role against AD. The GSTP1*B (P = .009) and GSTP1*C (P = .011) allelic variants were associated with increase in AD risk.
  
  
  CONCLUSIONS
  This study demonstrates that the GSTP1*B and *C allelic variants may be considered a candidate gene for AD. It can be suggested that although CYP2D6*4 polymorphism is not a risk of AD, the CYP2D6*4 and GSTP1 polymorphism may interact with β-HCH, dieldrin, and copper to influence the risk of AD.
authors.affiliation: Department of Neurochemistry, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India.
authors.forename: Neeraj Kumar
authors.initials: NK
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, Environmental Biochemistry Laboratory, University College of Medical Science & G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi, India.
authors.forename: B D
authors.initials: BD
authors.lastname: Banerjee
authors.affiliation: Department of Neurology, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Bala
authors.affiliation: Health Centre, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India.
authors.forename: Mitra
authors.initials: M
authors.lastname: Basu
authors.affiliation: Department of Neurochemistry, Institute of Human Behaviour and Allied Sciences, Dilshad Garden, Delhi, India nlmchhillar@yahoo.co.in.
authors.forename: Neelam
authors.initials: N
authors.lastname: Chhillar
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002849:Chromatography, Gas; D003300:Copper / Q000097:blood; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004026:Dieldrin / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D001556:Hexachlorocyclohexane / Q000097:blood; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood*; D008274:Magnesium / Q000097:blood; D008297:Male; D008875:Middle Aged; D010575:Pesticides / Q000097:blood*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D006843:Hydrocarbons, Chlorinated; D010575:Pesticides; D001556:Hexachlorocyclohexane; D003300:Copper; D019389:Cytochrome P-450 CYP2D6; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D004026:Dieldrin; D008274:Magnesium; C023888:beta-hexachlorocyclohexane
keywords: GSTP1 *B and *C allelic variants; dieldrin; neurodegenerative disease; serum copper; serum magnesium; β-hexachlorocyclohexane