Top

Neurological Sciences

Published in:

01-12-2019 | Alzheimer's Disease | Original Article

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

Authors: Yuxuan Song, Yi Lu, Zhen Liang, Yongjiao Yang, Xiaoqiang Liu

Published in: Neurological Sciences | Issue 12/2019

Abstract

Background

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).

Results

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.

Conclusions

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.

Pedersen NL (2010) Reaching the limits of genome-wide significance in Alzheimer disease. JAMA 303:1864CrossRef

Lane CA, Hardy J, Schott JM (2018) Alzheimer’s disease. Eur J Neurol 25:59–70CrossRef

(2016) 2016 Alzheimer’s disease facts and figures. Alzheimers Dement 12:459–509

Prince M, Ali G, Guerchet M, Prina AM, Albanese E, Wu Y (2016) Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther 8:23CrossRef

Loy CT, Schofield PR, Turner AM, Kwok JB (2014) Genetics of dementia. Lancet 383:828–840CrossRef

Green RC, Cupples LA, Go R, Benke KS, Edeki T, Griffith PA, Williams M, Hipps Y, Graff-Radford N, Bachman D, Farrer LA (2002) Risk of dementia among white and African American relatives of patients with Alzheimer disease. JAMA 287:329–336CrossRef

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 71:1183–1191CrossRef

Goodman Y, Bruce AJ, Cheng B, Mattson MP (1996) Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J Neurochem 66:1836–1844CrossRef

Toran-Allerand CD, Miranda RC, Bentham WD, Sohrabji F, Brown TJ, Hochberg RB, MacLusky NJ (1992) Estrogen receptors colocalize with low-affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain. Proc Natl Acad Sci U S A 89:4668–4672CrossRef

10.

Luine VN (1985) Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats. Exp Neurol 89:484–490CrossRef

11.

Jaffe AB, Toran-Allerand CD, Greengard P, Gandy SE (1994) Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. J Biol Chem 269:13065PubMed

12.

Murphy AJ, Guyre PM, Pioli PA (2010) Estradiol suppresses NF-kappa B activation through coordinated regulation of let-7a and miR-125b in primary human macrophages. J Immunol 184:5029–5037CrossRef

13.

Brann DW, Krishnan D, Chandramohan W, Mahesh VB, Khan MM (2007) Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 72:381–405CrossRef

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 80:807–814

15.

Simpkins JW, Dykens JA (2010) Mitochondrial mechanisms of estrogen neuroprotection. BBA - Gen Subjects 1800:1113–1120CrossRef

16.

Azcoitia I, Yague JG, Garcia-Segura LM (2011) Estradiol synthesis within the human brain. Neuroscience 191:139–147CrossRef

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 55:309–314CrossRef

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–e34CrossRef

19.

Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605CrossRef

20.

Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMed

21.

Dersimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRef

22.

Hayashino Y, Noguchi Y, Fukui T (2005) Systematic evaluation and comparison of statistical tests for publication bias. J Epidemiol 15:235–243CrossRef

23.

Chen LH, Fan YH, Kao PYP, Ho DTY, Ha JCT, Chu LW, Song Y (2017) Genetic polymorphisms in estrogen metabolic pathway associated with risks of Alzheimer's disease: evidence from a southern Chinese population. J Am Geriatr Soc 65:332–339CrossRef

24.

Zheng J, Yan H, Shi L, Kong Y, Zhao Y, Xie L, Li J, Huang M, Li J, Zhao S (2016) The CYP19A1 rs3751592 variant confers susceptibility to Alzheimer disease in the Chinese Han population. Medicine. 95:e4742CrossRef

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 22:216–220CrossRef

26.

Chace C, Pang D, Weng C, Temkin A, Lax S, Silverman W, Zigman W, Ferin M, Lee JH, Tycko B, Schupf N (2012) Variants in CYP17 and CYP19 cytochrome P450 genes are associated with onset of Alzheimer’s disease in women with down syndrome. J Alzheimers Dis 28:601–612CrossRef

27.

Butler HT, Warden DR, Hogervorst E, Ragoussis J, Smith AD, Lehmann DJ (2010) Association of the aromatase gene with Alzheimer’s disease in women. Neurosci Lett 468:202–206CrossRef

28.

Combarros O, Sánchez-Juan P, Riancho JA, Mateo I, Rodríguez-Rodríguez E, Infante J, García-Gorostiaga I, Vázquez-Higuera JL, Berciano J (2008) Aromatase and interleukin-10 genetic variants interactively modulate Alzheimer’s disease risk. J Neural Transm 115:863–867CrossRef

29.

Huang R (2006) CYP19 haplotypes increase risk for Alzheimer’s disease. J Med Genet 43:e42CrossRef

30.

Iivonen S, Corder E, Lehtovirta M, Helisalmi S, Mannermaa A, Vepsäläinen S, Hänninen T, Soininen H, Hiltunen M (2004) Polymorphisms in the CYP19 gene confer increased risk for Alzheimer disease. Neurology 62:1170–1176CrossRef

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 53:36–47CrossRef

32.

Zhang J, Yin Y, Niu XM, Liu Y, Garfield D, Chen SF, Wang R, Wang L, Chen HQ (2013) CYP19A1 gene polymorphisms and risk of lung cancer. J Int Med Res 41:735–742CrossRef

33.

Yi K, Yang L, Lan Z, Xi M (2016) The association between CYP19 polymorphism and endometriosis risk: a system review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 199:42–48CrossRef

34.

Wang B, Fu ZY, Ma YT, Huang D, Liu F, Dong CL, Wang T, Meng YJ (2016) Identification of a CYP19 gene single-nucleotide polymorphism associated with a reduced risk of coronary heart disease. Genet Test Mol Biomarkers 20:2–10CrossRef

35.

Fu YZ, Wang B, Ma TY, Huang D, Liu F, Dong LC, Wang T, Meng JY (2016) A novel polymorphism of the CYP19 gene is associated with essential hypertension in China. Clin Lab 62:195–202PubMed

36.

Zins K, Mogg M, Schneeberger C, Abraham D, Schreiber M (2014) Analysis of the rs10046 polymorphism of aromatase (CYP19) in premenopausal onset of human breast cancer. Int J Mol Sci 15:712–724CrossRef

37.

Zheng H, Xu H, Uljon SN, Gross R, Hardy K, Gaynor J, Lafrancois J, Simpkins J, Refolo LM, Petanceska S, Wang R, Duff K (2002) Modulation of A (beta) peptides by estrogen in mouse models. J Neurochem 80:191–196CrossRef

38.

Petanceska SS, Nagy V, Frail D, Gandy S (2000) Ovariectomy and 17beta-estradiol modulate the levels of Alzheimer's amyloid beta peptides in brain. Neurology 54:2212–2217CrossRef

Title: 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
Authors: Yuxuan Song
Yi Lu
Zhen Liang
Yongjiao Yang
Xiaoqiang Liu
Publication date: 01-12-2019
Publisher: Springer International Publishing
Keywords: Alzheimer's Disease
Alzheimer's Disease
Estrogens
Published in: Neurological Sciences / Issue 12/2019
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-019-04003-1

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Background

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2019

A case of recurrent vomiting: extending the spectrum of neuronal intranuclear inclusion disease

Impact of opium dependency on clinical and neuropsychological indices of multiple sclerosis patients

Non-motor symptoms of Parkinson’s disease: dopaminergic basis or not?

Headache and vision loss in a middle-aged women

The clinical utility of non-invasive video-electroencephalographic monitoring has been diversifying

Vitamin D in migraine headache: a comprehensive review on literature