Association between rs10046, rs1143704, rs767199, rs727479, rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms in aromatase (CYP19A1) gene and Alzheimer’s disease risk: a systematic review and meta-analysis involving 11,051 subjects
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CYP19A1 enzyme (aromatase) encoded by CYP19A1 (cytochrome p450 family 19 subfamily a member 1) gene plays a key role in the biosynthesis of estrogen, which has been significantly associated with Alzheimer’s disease (AD). To ascertain whether CYP19A1 gene polymorphisms are correlated with the susceptibility to AD, we performed this systematic review and meta-analysis of currently available studies.
Materials and methods
A comprehensive literature search was conducted by using PubMed, Embase, and Web of Science databases and the Cochrane Library. The association was evaluated by using odds ratios (ORs) and 95% confidence intervals (CIs) through Stata software (version 12.0).
A total of eight articles including 39 case–control studies with 11,051 subjects including 3215 AD cases and 7836 controls were involved in this meta-analysis. By pooling all eligible studies, we detected that rs10046, rs1143704, rs767199, and rs727479 polymorphisms in CYP19A1 gene were significantly associated with AD risk. A significant association between rs10046 polymorphism and AD risk was found under allele contrast, homozygous (TT vs CC: OR = 1.17, 95%CI = 1.02–1.34, I2 = 0.0%, P = 0.026), and dominant genetic models. In addition, we observed an association between with rs1143704 polymorphism under heterozygous and dominant genetic models (TT+TA vs AA: OR = 1.36, 95%CI = 1.03–1.79, I2 = 0.0%, P = 0.033). Similar results were found in rs767199 and rs727479 polymorphisms, while null results were found for other polymorphisms.
This systematic review and meta-analysis suggested that the rs10046, rs1143704, rs767199, and rs727479 polymorphisms in CYP19A1 gene significantly increase AD susceptibility. In addition, our results demonstrated that homozygous TT genotype in rs10046, dominant AA and AG genotypes in rs767199, homozygous TT genotype in rs727479, and dominant TT and TA genotypes in rs1143704 might be the susceptibility genotypes for AD, while no associations were observed between rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms and AD susceptibility.
KeywordsAromatase Alzheimer’s disease Polymorphism Systematic review Meta-analysis
This work was supported by the Tianjin Natural Science Foundation of China (16JCZDJC34600).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 3.(2016) 2016 Alzheimer’s disease facts and figures. Alzheimers Dement 12:459–509Google Scholar
- 7.Lautner R, Palmqvist S, Mattsson N, Andreasson U, Wallin A, Pålsson E, Jakobsson J, Herukka S, Owenius R, Olsson B, Hampel H, Rujescu D, Ewers M, Landén M, Minthon L, Blennow K, Zetterberg H, Hansson O (2014) Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease. Jama Psychiat 71:1183–1191CrossRefGoogle Scholar
- 14.Zhe L, Jon V, Sepideh SH, Joseph R, Rena L (2010) Effects of estrogen treatment on glutamate uptake in cultured human astrocytes derived from cortex of Alzheimer’s disease patients. J Neurochem 80:807–814Google Scholar
- 17.Nicola N, Antonella R, Cynthia M, Jayasree Y, Swapna V, Gerard M, Tusar G, Cheryl M, Vibhati K, Clifford Q (2013) Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with aromatase inhibitor associated bone loss in women with ER + breast cancer. Bone 55:309–314CrossRefGoogle Scholar
- 18.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–e34CrossRefGoogle Scholar
- 25.Medway C, Combarros O, Cortina-Borja M, Butler HT, Ibrahim-Verbaas CA, de Bruijn RFAG, Koudstaal PJ, van Duijn CM, Ikram MA, Mateo I, Sánchez-Juan P, Lehmann MG, Heun R, Kölsch H, Deloukas P, Hammond N, Coto E, Alvarez V, Kehoe PG, Barber R, Wilcock GK, Brown K, Belbin O, Warden DR, Smith AD, Morgan K, Lehmann DJ (2014) The sex-specific associations of the aromatase gene with Alzheimer’s disease and its interaction with IL10 in the Epistasis Project. Eur J Hum Genet 22:216–220CrossRefGoogle Scholar
- 31.Lunnon K, Keohane A, Pidsley R, Newhouse S, Riddoch-Contreras J, Thubron EB, Devall M, Soininen H, Kloszewska I, Mecocci P, Tsolaki M, Vellas B, Schalkwyk L, Dobson R, Malik AN, Powell J, Lovestone S, Hodges A (2017) Mitochondrial genes are altered in blood early in Alzheimer’s disease. Neurobiol Aging 53:36–47CrossRefGoogle Scholar