title: Genetic Polymorphisms in Estrogen Metabolic Pathway Associated with Risks of Alzheimer's Disease: Evidence from a Southern Chinese Population.
abstract: OBJECTIVE
  To investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease (AD).
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Individuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong.
  
  
  METHODS
  Chinese individuals with (n = 426) and without (n = 350) AD.
  
  
  METHODS
  All subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor α gene (ESR1), estrogen receptor β gene (ESR2), cytochrome P450 19A1 gene (CYP19A1), cytochrome P450 11A1 gene (CYP11A1)).
  
  
  RESULTS
  Apart from consistent results showing an association between apolipoprotein (APO)E and AD, strong evidence of disease associations were found for polymorphisms in ESR2 and CYP11A1 based on the entire data set. For ESR2, significant protective effects were found for A alleles of rs4986938 (permuted P = .02) and rs867443 (permuted P = .02). For CYP11A1, significant risk effects were found for G alleles of rs11638442 (permuted P = .03) and rs11632698 (permuted P = .03). Stratifying subjects according to APOE ε4 status, their genetic effects continued to be significant in the APOE ε4-negative subgroup. Associations between CYP11A1 polymorphisms (rs2279357, rs2073475) and risk of AD were detected in women but not men. Further gene-level analysis confirmed the above association between ESR2 and CYP11A1, and pathway-level analysis highlighted the genetic effect of the estrogen metabolic pathway on disease susceptibility (permuted pathway-level P = .03).
  
  
  CONCLUSIONS
  Consistent with previous biological findings for sex steroid hormones in the central nervous system, genetic alterations on the estrogen metabolic pathway were revealed in the Chinese population. Confirmation of these present findings in an independent population is warranted to elucidate disease pathogenesis and to explore the potential of hormone therapy in the treatment of AD.
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.|Department of Psychology, Faculty of Social Sciences, University of Hong Kong, Hong Kong.|Division of Geriatric Medicine, Department of Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Lu Hua
authors.initials: LH
authors.lastname: Chen
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.|Centre for Genomic Sciences, University of Hong Kong, Hong Kong.
authors.forename: Yan Hui
authors.initials: YH
authors.lastname: Fan
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Patrick Yu Ping
authors.initials: PY
authors.lastname: Kao
authors.affiliation: Division of Geriatric Medicine, Department of Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Deborah Tip Yin
authors.initials: DT
authors.lastname: Ho
authors.affiliation: Division of Geriatric Medicine, Department of Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Joyce Cheuk Tung
authors.initials: JC
authors.lastname: Ha
authors.affiliation: Division of Geriatric Medicine, Department of Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.|Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.|Alzheimer's Disease Research Network, Strategic Research Theme on Aging, University of Hong Kong, Hong Kong.|State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong.
authors.forename: Leung Wing
authors.initials: LW
authors.lastname: Chu
authors.affiliation: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.|Alzheimer's Disease Research Network, Strategic Research Theme on Aging, University of Hong Kong, Hong Kong.|State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong.
authors.forename: You-Qiang
authors.initials: YQ
authors.lastname: Song
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003430:Cross-Sectional Studies; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006723:Hong Kong; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
chemical_list: D001054:Apolipoproteins A; C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta; C022205:apolipoprotein A-IV; D002786:Cholesterol Side-Chain Cleavage Enzyme
keywords: Alzheimer's disease; estrogen metabolic pathway; polymorphisms