CYP46A1 intron-2T/C polymorphism and Alzheimer's disease: An updated meta-analysis of 16 studies including 3960 cases and 3828 controls

• A total of 3960 cases and 3828 controls in 16 case–control studies were included.
• The combined results showed that there were no significant differences in genotype distribution between cases and controls.
• In the subgroup analysis, significant associations were detected neither in Caucasians nor in Asians.
• Our results imply the CYP46A1 intron-2T/C (rs754203) polymorphism may be a minor risk factor for AD susceptibility.

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 I2 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.