title: CYP46A1 intron-2T/C polymorphism and Alzheimer's disease: an updated meta-analysis of 16 studies including 3,960 cases and 3,828 controls.
abstract: Whether the variations in the cholesterol 24S-hydroxylase (CYP46A1) gene would raise Alzheimer's risk is still undetermined. A previous meta-analysis about the association between AD susceptibility and CYP46A1 intron-2T/C (rs754203) has led to inconsistent conclusions. To assess the relationship between the CYP46A1 rs754203 polymorphism and AD risk more exactly, relevant literature was recruited by searching the Cochrane Library, PubMed, Medline (Ovid), Embase (Ovid), ISI Web of Science, the Chinese Biomedicine Database (CBM), CNKI, Wan fang, and reference lists of articles. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using fixed and random effects models, publication bias was tested by funnel plot and Egger's test, heterogeneity was assessed with I(2) statistics. Sixteen case-control studies were included with a total of 7788 individuals, involving 3960 AD patients and 3828 controls. The combined results showed no significant differences in allele comparison C vs. T (OR=1.04, 95% CI=0.86-1.26), recessive model CC vs. TC+TT (OR=1.24, 95% CI=0.90-1.69) and dominant model CC+TC vs. TT (OR=1.03, 95% CI=0.84-1.27). When stratifying for ethnicity, no significant associations were detected in Caucasians or in Asians. Our results suggested that CYP46A1 rs754203 is a minor risk factor for AD. However, more wide samples of highly selected AD patients, based on different onset age and other confirmed genetic factors interactions, are needed to clarify these association and further researches should be carried out to explore the effect of genetic networks, environmental factors, individual biological characteristics and their mutual interactions.
authors.affiliation: Department of Neurology, The Second Hospital Affiliated to Nanchang University, No. 1, Minde Road, Nanchang, Jiangxi 330006, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Shen
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Tang
mesh_terms: D017668:Age of Onset; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D000072556:Cholesterol 24-Hydroxylase; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D011110:Polymorphism, Genetic; D013250:Steroid Hydroxylases / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase
keywords: Alzheimer's disease; CYP46A1; Meta-analysis; Polymorphism