The sex-specific associations of the aromatase gene with Alzheimer's disease and its interaction with IL10 in the Epistasis Project

European Journal of Human Genetics

Volumn 22, Issue 2, 2014, Pages 216-220

  Medway, Christopher ^a   Combarros, Onofre ^b   Cortina Borja, Mario ^c   Butler, Helen T ^d   Ibrahim Verbaas, Carla A ^e   De Bruijn, Renée F A G ^e   Koudstaal, Peter J ^e   Van Duijn, Cornelia M ^e   Ikram, M Arfan ^e   Mateo, Ignacio ^b   Sánchez Juan, Pascual ^b   Lehmann, Michael G ^f   Heun, Reinhard ^g,h   Kölsch, Heike ^g   Deloukas, Panos ⁱ   Hammond, Naomi ⁱ   Coto, Eliecer ^j   Alvarez, Victoria ^j   Kehoe, Patrick G ^k   Barber, Rachel ^k   Wilcock, Gordon K ^l   Brown, Kristelle ^a   Belbin, Olivia ^a   Warden, Donald R ^f   Smith, A David ^f   Morgan, Kevin ^f   Lehmann, Donald J ⁱ   more..

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b UNIVERSITY OF CANTABRIA   (Spain)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e ERASMUS MEDICAL CENTER   (Netherlands)

^f UNIVERSITY OF OXFORD   (United Kingdom)

^g UNIVERSITY OF BONN   (Germany)

^h ROYAL DERBY HOSPITAL   (United Kingdom)

ⁱ WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^j HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS   (Spain)

^k UNIVERSITY OF BRISTOL   (United Kingdom)

^l UNIVERSITY OF OXFORD   (United Kingdom)

more..

Author keywords

C18; dementia; healthy cell bias; neurodegeneration

Indexed keywords

AROMATASE; ESTROGEN; INTERLEUKIN 10; CYP19A1 PROTEIN, HUMAN; IL10 PROTEIN, HUMAN;

AGED; ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; EPISTASIS; ESTROGEN BLOOD LEVEL; ESTROGEN SYNTHESIS; FEMALE; GENE FREQUENCY; GENE INTERACTION; GENE LINKAGE DISEQUILIBRIUM; GENE MUTATION; GENETIC ASSOCIATION; GENETIC RISK; GENOTYPE; HUMAN; INTRON; MAJOR CLINICAL STUDY; MALE; NERVE DEGENERATION; NEUROPROTECTION; POPULATION; POSTMENOPAUSE; PRIORITY JOURNAL; RISK ASSESSMENT; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; VERY ELDERLY; CASE CONTROL STUDY; ENZYMOLOGY; GENETIC PREDISPOSITION; GENETICS; RISK; SEXUAL DEVELOPMENT;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; AROMATASE; CASE-CONTROL STUDIES; EPISTASIS, GENETIC; FEMALE; GENE FREQUENCY; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; INTERLEUKIN-10; LINKAGE DISEQUILIBRIUM; MALE; ODDS RATIO; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK; SEX CHARACTERISTICS;

EID: 84892779848     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2013.116     Document Type: Article

References (74)

1. Stoffel-Wagner B: Neurosteroid biosynthesis in the human brain and its clinical implications. Ann N Y Acad Sci 2003; 1007: 64-78.
2. Ishunina TA, Van Beurden D, Van der Meulen G et al: Diminished aromatase immunoreactivity in the hypothalamus, but not in the basal forebrain nuclei in Alzheimer's disease. Neurobiol Aging 2005; 26: 173-194.
3. Yague JG, Muñoz A, De Monasterio-Schrader P, Defelipe J, Garcia-Segura LM, Azcoitia I: Aromatase expression in the human temporal cortex. Neuroscience 2006; 138: 389-401.
4. Ishunina TA, Fischer DF, Swaab DF: Estrogen receptor alpha and its splice variants in the hippocampus in aging and Alzheimer's disease. Neurobiol Aging 2007; 28: 1670-1681.
5. Luchetti S, Bossers K, Van de Bilt S et al: Neurosteroid biosynthetic pathways changes in prefrontal cortex in Alzheimer's disease. Neurobiol Aging 2011; 32: 1964-1976.
6. Azcoitia I, Sierra A, Veiga S, Garcia-Segura LM: Aromatase expression by reactive astroglia is neuroprotective. Ann N Y Acad Sci 2003; 1007: 298-305.
7. Brann DW, Dhandapani K, Wakade C, Mahesh VB, Khan MM: Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids 2007; 72: 381-405.
8. Fiocchetti M, Ascenzi P, Marino M: Neuroprotective effects of 17b-estradiol rely on estrogen receptor membrane initiated signals. Front Physiol 2012; 3: 73.
9. Wang JM, Liu L, Brinton RD: Estradiol-17beta-induced human neural progenitor cell proliferation is mediated by an estrogen receptor beta-phosphorylated extracellularly regulated kinase pathway. Endocrinology 2008; 149: 208-218.
10. Shao B, Cheng Y, Jin K: Estrogen, neuroprotection and neurogenesis after ischemic stroke. Curr Drug Targets 2012; 13: 188-198.
11. Liang Z, Valla J, Sefidvash-Hockley S, Rogers J, Li R: Effects of estrogen treatment on glutamate uptake in cultured human astrocytes derived from cortex of Alzheimer's disease patients. J Neurochem 2002; 80: 807-814.
12. Simpkins JW, Yi KD, Yang S-H, Dykens JA: Mitochondrial mechanisms of estrogen neuroprotection. Biochim Biophys Acta 2010; 1800: 1113-1120.
13. Numakawa T, Matsumoto T, Numakawa Y, Richards M, Yamawaki S, Kunugi H: Protective action of neurotrophic factors and estrogen against oxidative stress-mediated neurodegeneration. J Toxicol 2011; 2011: 405194.
14. Kramer PR, Kramer SF, Guan G: 17 beta-estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte-derived macrophages. Arthritis Rheum 2004; 50: 1967-1975.
15. Cvoro A, Tatomer D, Tee M-K, Zogovic T, Harris HA, Leitman DC: Selective estrogen receptor-beta agonists repress transcription of proinflammatory genes. J Immunol 2008; 180: 630-636.
16. Murphy AJ, Guyre PM, Pioli PA: Estradiol suppresses NF-kappa B activation through coordinated regulation of let-7a and miR-125b in primary human macrophages. J Immunol 2010; 184: 5029-5037.
17. Bengtsson AK, Ryan EJ, Giordano D, Magaletti DM, Clark EA: 17beta-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells. Blood 2004; 104: 1404-1410.
18. Azcoitia I, Arevalo M-A, De Nicola AF, Garcia-Segura LM: Neuroprotective actions of estradiol revisited. Trends Endocrinol Metab 2011; 22: 467-473.
19. Selvamani A, Sohrabji F: Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats. Neurobiol Aging 2010; 31: 1618-1628.
20. Selvamani A, Sohrabji F: The neurotoxic effects of estrogen on ischemic stroke in older female rats is associated with age-dependent loss of insulin-like growth factor-1. J Neurosci 2010; 30: 6852-6861.
21. Gillies GE, McArthur S: Estrogen actions in the brain and the basis for differential action in men and women: a case for sex-specific medicines. Pharmacol Rev 2010; 62: 155-198.
22. Iivonen S, Corder E, Lehtovirta M et al: Polymorphisms in the CYP19 gene confer increased risk for Alzheimer disease. Neurology 2004; 62: 1170-1176.
23. Combarros O, Riancho JA, Infante J et al: Interaction between CYP19 aromatase and butyrylcholinesterase genes increases Alzheimer's disease risk. Dement Geriatr Cogn Disord 2005; 20: 153-157.
24. Combarros O, Sánchez-Juan P, Riancho JA et al: Aromatase and interleukin-10 genetic variants interactively modulate Alzheimer's disease risk. J Neural Transm 2008; 115: 863-867.
25. Huang R, Poduslo SE: CYP19 haplotypes increase risk for Alzheimer's disease. J Med Genet 2006; 43: e42.
26. Corbo RM, Gambina G, Ulizzi L, Moretto G, Scacchi R: Genetic variation of CYP19 (aromatase) gene influences age at onset of Alzheimer's disease in women. Dement Geriatr Cogn Disord 2009; 27: 513-518.
27. Butler HT, Warden DR, Hogervorst E, Ragoussis J, Smith AD, Lehmann DJ: Association of the aromatase gene with Alzheimer's disease in women. Neurosci Lett 2010; 468: 202-206.
28. Dimayuga FO, Reed JL, Carnero GA et al: Estrogen and brain inflammation: effects on microglial expression of MHC, costimulatory molecules and cytokines. J Neuroimmu-nol 2005; 161: 123-136.
29. Yates MA, Li Y, Chlebeck PJ, Offner H: GPR30, but not estrogen receptor-alpha, is crucial in the treatment of experimental autoimmune encephalomyelitis by oral ethinyl estradiol. BMC Immunol 2010; 11: 20.
30. De Medeiros SF, Maitelli A: Cellular and humoral immune responses after short-term oral hormone therapy in postmenopausal women. Climacteric 2011; 14: 677-682.
31. Velders M, Schleipen B, Fritzemeier KH, Zierau O, Diel P: Selective estrogen receptor-b activation stimulates skeletal muscle growth and regeneration. FA S E B J 2012; 26: 1909-1920.
32. Combarros O, Van Duijn CM, Hammond N et al: Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease. J Neuroinflammation 2009; 6: 22.
33. Mirra SS, Heyman A, McKeel D et al: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 1991; 41: 479-486.
34. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984; 34: 939-944.
35. Kölsch H, Lehmann DJ, Ibrahim-Verbaas CA et al: Interaction of insulin and PPAR-a genes in Alzheimer's disease: the Epistasis Project. J Neural Transm 2012; 119: 473-479.
36. Cortina-Borja M, Smith AD, Combarros O, Lehmann DJ: The synergy factor: a statistic to measure interactions in complex diseases. BMC Res Notes 2009; 2: 105.
37. Ovcharenko I, Nobrega MA, Loots GG, Stubbs L: ECR Browser: a tool for visualizing and accessing data from comparisons of multiple vertebrate genomes. Nucleic Acids Res 2004; 32: W280-W286.
38. Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120: 15-20.
39. Ward LD, Kellis M: HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 2012; 40: D930-D934.
40. Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 2010; 467: 1061-1073.
41. Johnson AD, Handsaker RE, Pulit SL, Nizzari MM, O'Donnell CJ, De Bakker PIW: SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 2008; 24: 2938-2939.
42. Ma SL, Tang NLS, Lam LCW, Chiu HFK: The association between promoter polymorphism of the interleukin-10 gene and Alzheimer's disease. Neurobiol Aging 2005; 26: 1005-1010.
43. Bagnoli S, Cellini E, Tedde A et al: Association of IL10 promoter polymorphism in Italian Alzheimer's disease. Neurosci Lett 2007; 418: 262-265.
44. Czonkowska A, Ciesielska A, Gromadzka G, Kurkowska-Jastrzebska I: Gender differences in neurological disease: role of estrogens and cytokines. Endocrine 2006; 29: 243-256.
45. Wyss-Coray T: Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 2006; 12: 1005-1015.
46. Rosario ER, Chang L, Head EH, Stanczyk FZ, Pike CJ: Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer's disease. Neurobiol Aging 2011; 32: 604-613.
47. Brown CM, Mulcahey TA, Filipek NC, Wise PM: Production of proinflammatory cytokines and chemokines during neuroinflammation: novel roles for estrogen receptors alpha and beta. Endocrinology 2010; 151: 4916-4925.
48. Srivastava S, Weitzmann MN, Cenci S, Ross FP, Adler S, Pacifici R: Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD. J Clin Invest 1999; 104: 503-513.
49. Bryant DN, Sheldahl LC, Marriott LK, Shapiro RA, Dorsa DM: Multiple pathways transmit neuroprotective effects of gonadal steroids. Endocrine 2006; 29: 199-207.
50. Vest RS, Pike CJ: Gender, sex steroid hormones, and Alzheimer's disease. Horm Behav 2012; 63: 301-307.
51. Brinton RD: Estrogen regulation of glucose metabolism and mitochondrial function: therapeutic implications for prevention of Alzheimer's disease. Adv Drug Deliv Rev 2008; 60: 1504-1511.
52. Letenneur L, Gilleron V, Commenges D, Helmer C, Orgogozo JM, Dartigues JF: Are sex and educational level independent predictors of dementia and Alzheimer's disease? Incidence data from the PAQUID project. J Neurol Neurosurg Psychiatry 1999; 66: 177-183.
53. Azad NA, Al Bugami M, Loy-English I: Gender differences in dementia risk factors. Gender medicine 2007; 4: 120-129.
54. Ramirez-Lorca R, Grilo A, Martinez-Larrad MT et al: Sex and body mass index specific regulation of blood pressure by CYP19A1 gene variants. Hypertension 2007; 50: 884-890.
55. Elias MF, Wolf PA, D'Agostino RB, Cobb J, White LR: Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. Am J Epidemiol 1993; 138: 353-364.
56. Kivipelto M, Helkala E-L, Laakso MP et al: Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002; 137: 149-155.
57. Yue X, Lu M, Lancaster T et al: Brain estrogen deficiency accelerates Abeta plaque formation in an Alzheimer's disease animal model. Proc Natl Acad Sci USA 2005; 102: 19198-19203.
58. Kretz O, Fester L, Wehrenberg U et al: Hippocampal synapses depend on hippocampal estrogen synthesis. J Neurosci 2004; 24: 5913-5921.
59. Mukai H, Kimoto T, Hojo Y et al: Modulation of synaptic plasticity by brain estrogen in the hippocampus. Biochim Biophys Acta 2010; 1800: 1030-1044.
60. Overk CR, Lu P-Y, Wang Y-T et al: Effects of aromatase inhibition versus gonadectomy on hippocampal complex amyloid pathology in triple transgenic mice. Neurobiol Dis 2012; 45: 479-487.
61. Brinton RD: The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications. Trends Neurosci 2008; 31: 529-537.
62. Craig MC, Maki PM, Murphy DGM: The Women's Health Initiative Memory Study: findings and implications for treatment. Lancet Neurol 2005; 4: 190-194.
63. Hogervorst E, Bandelow S: The controversy over levels of sex steroids in cases with Alzheimer's disease. J Neuroendocrinol 2004; 16: 93-94.
64. Fratiglioni L, Viitanen M, Von Strauss E, Tontodonati V, Herlitz A, Winblad B: Very old women at highest risk of dementia and Alzheimer's disease: incidence data from the Kungsholmen Project, Stockholm. Neurology 1997; 48: 132-138.
65. Ott A, Breteler MM, Van Harskamp F, Stijnen T, Hofman A: Incidence and risk of dementia. The Rotterdam Study. Am J Epidemiol 1998; 147: 574-580.
66. Matthews F, Brayne C: The incidence of dementia in England and Wales: findings from the five identical sites of the MRC CFA Study. PLoS Med 2005; 2: e193.
67. Zhang Y, Zhang J, Tian C et al: The-1082G/A polymorphism in IL-10 gene is associated with risk of Alzheimer's disease: a meta-analysis. J Neurol Sci 2011; 303: 133-138.
68. Di Bona D, Rizzo C, Bonaventura G, Candore G, Caruso C: Association between interleukin-10 polymorphisms and Alzheimer's disease: a systematic review and meta-analysis. J Alzheimers Dis 2012; 29: 751-759.
69. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV: An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1-8.
70. Dunning AM, Dowsett M, Healey CS et al: Polymorphisms associated with circulating sex hormone levels in postmenopausal women. J Natl Cancer Inst 2004; 96: 936-945.
71. Tworoger SS, Chubak J, Aiello EJ et al: Association of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women. Cancer Epidemiol Biomarkers Prev 2004; 13: 94-101.
72. Haiman CA, Dossus L, Setiawan VW et al: Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women. Cancer Res 2007; 67: 1893-1897.
73. Kristensen VN, Harada N, Yoshimura N et al: Genetic variants of CYP19 (aromatase) and breast cancer risk. Oncogene 2000; 19: 1329-1333.
74. Wang JZ, Deogan MS, Lewis JR et al: A non-synonymous coding change in the CYP19A1 gene Arg264Cys (rs700519) does not affect circulating estradiol, bone structure or fracture. BMC Med Genet 2011; 12: 165.