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Genetic Polymorphisms in Estrogen Metabolic Pathway Associated with Risks of Alzheimer's Disease: Evidence from a Southern Chinese Population
Author(s) -
Chen Lu Hua,
Fan Yan Hui,
Kao Patrick Yu Ping,
Ho Deborah Tip Yin,
Ha Joyce Cheuk Tung,
Chu Leung Wing,
Song YouQiang
Publication year - 2017
Publication title -
journal of the american geriatrics society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.992
H-Index - 232
eISSN - 1532-5415
pISSN - 0002-8614
DOI - 10.1111/jgs.14537
Subject(s) - medicine , apolipoprotein e , estrogen , allele , genotyping , genetics , genetic predisposition , bioinformatics , disease , endocrinology , genotype , gene , biology
Objectives To investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease ( AD ). Design Cross‐sectional study. Setting Individuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong. Participants Chinese individuals with (n = 426) and without (n = 350) AD . Measurements All subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor α gene ( ESR 1), estrogen receptor β gene ( ESR 2), cytochrome P450 19A1 gene ( CYP 19A1), cytochrome P450 11A1 gene ( CYP 11A1)). Results Apart from consistent results showing an association between apolipoprotein ( APO )E and AD , strong evidence of disease associations were found for polymorphisms in ESR 2 and CYP 11A1 based on the entire data set. For ESR 2, significant protective effects were found for A alleles of rs4986938 (permuted P = .02) and rs867443 (permuted P = .02). For CYP 11A1, significant risk effects were found for G alleles of rs11638442 (permuted P = .03) and rs11632698 (permuted P = .03). Stratifying subjects according to APOE ε 4 status, their genetic effects continued to be significant in the APOE ε 4‐negative subgroup. Associations between CYP 11A1 polymorphisms (rs2279357, rs2073475) and risk of AD were detected in women but not men. Further gene‐level analysis confirmed the above association between ESR 2 and CYP 11A1, and pathway‐level analysis highlighted the genetic effect of the estrogen metabolic pathway on disease susceptibility (permuted pathway‐level P = .03). Conclusion 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 .