title: Association study of two steroid biosynthesis genes (COMT and CYP17) with Alzheimer's disease in the Italian population.
abstract: The greater predisposition of women to Alzheimer's disease (AD), owing to the decrease in postmenopausal estrogen, may be influenced by polymorphic variation in genes regulating estrogen metabolism (e.g., COMT) and estrogen biosynthesis (e.g., CYP17). In order to better understand how the estrogen pathway genetic variation might affect AD onset, we conducted a case-control study of two single nucleotide polymorphisms (SNPs) of these two genes (COMT rs4680 and CYP17 rs743572) in a sample of AD patients of Italian origin. The COMT allele and genotype were found associated neither with AD onset nor with parameters of AD severity, such as cognitive impairment, age at onset, or disease duration. In contrast, CYP17 was found to affect the age at disease onset mainly in males and, as compared with noncarriers, people carrying the A2 (C) allele had a 2.2-fold increased risk for AD. These findings suggest that the CYP17 A2 allele influences AD susceptibility in a sex-specific way by acting not only on AD risk but also on the age at disease onset, an important parameter of AD severity.
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin", Sapienza University, Rome, Italy; CNR Institute of Cellular Biology and Neurobiology, Via E. Ramerini 32, 00015 Monterotondo Scalo, Rome, Italy. Electronic address: Rosamaria.Corbo@uniroma1.it.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Corbo
authors.affiliation: Alzheimer's Disease Center, Department of Neuroscience, University and Hospital of Verona, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gambina
authors.affiliation: Alzheimer's Disease Center, Department of Neuroscience, University and Hospital of Verona, Verona, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Broggio
authors.affiliation: CNR Institute of Cellular Biology and Neurobiology, Via E. Ramerini 32, 00015 Monterotondo Scalo, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Scarabino
authors.affiliation: CNR Institute of Molecular Biology and Pathology, c/o Department of Biology and Biotechnology "Charles Darwin", Sapienza University, Rome, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Scacchi
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008609:Mental Status Schedule; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D013254:Steroid 17-alpha-Hydroxylase; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Alzheimer's disease; COMT; CYP17; Estrogen; Genetic association