The CALHM1 P86L Polymorphism is a Genetic Modifier of Age at Onset in Alzheimer's Disease: a Meta-Analysis Study
JOURNAL OF ALZHEIMERS DISEASE
Authors: Lambert, Jean-Charles; Sleegers, Kristel; Gonzalez-Perez, Antonio; Ingelsson, Martin; Beecham, Gary W.; Hiltunen, Mikko; Combarros, Onofre; Bullido, Maria J.; Brouwers, Nathalie; Bettens, Karolien; Berr, Claudine; Pasquier, Florence; Richard, Florence; DeKosky, Steven T.; Hannequin, Didier; Haines, Jonathan L.; Tognoni, Gloria; Fievet, Nathalie; Dartigues, Jean-Francois; Tzourio, Christophe; Engelborghs, Sebastiaan; Arosio, Beatrice; Coto, Elicer; De Deyn, Peter; Del Zompo, Maria; Mateo, Ignacio; Boada, Merce; Antunez, Carmen; Lopez-Arrieta, Jesus; Epelbaum, Jacques; Schjcide, Brit-Marcn Michaud; Frank-Garcia, Ana; Gicdraitis, Vilmentas; Helisalmi, Seppo; Porcellini, Elisa; Pilotto, Alberto; Forti, Paola; Ferri, Raffaele; Delepine, Marc; Zelenika, Diana; Lathrop, Mark; Scarpini, Elio; Siciliano, Gabriele; Solfrizzi, Vincenzo; Sorbi, Sandro; Spalletta, Gianfranco; Ravaglia, Giovanni; Valdivieso, Fernando; Vepsalainen, Saila; Alvarez, Victoria; Bosco, Paolo; Mancuso, Michelangelo; Panza, Francesco; Nacmias, Benedetta; Bossu, Paola; Hanon, Olivier; Piccardi, Paola; Annoni, Giorgio; Mann, David; Marambaud, Philippe; Seripa, Davide; Galimberti, Daniela; Tanzi, Rudolph E.; Bertram, Lars; Lendon, Corinne; Lannfelt, Lars; Licastro, Federico; Campion, Dominique; Pericak-Vance, Margaret A.; Soininen, Hilkka; Van Broeckhoven, Christine; Alperovitch, Annick; Ruiz, Agustin; Kamboh, M. Ilyas; Amouyel, Philippe
Abstract
The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon 4 allele of the APOE gene.
Calcium homeostasis modulator 1 gene P86L polymorphism and the risk for alzheimer's disease: A meta-analysis
NEUROSCIENCE LETTERS
Authors: Mun, Myung-Jin; Kim, Jin-Ho; Choi, Ji-Young; Jang, Won-Cheoul
Abstract
Objectives: Recently, many epidemiological studies have demonstrated an association between P86L polymorphism of calcium homeostasis modulator 1 (CALHMI) and risk for Alzheimer's disease (AD). However, the results of these association studies are inconsistent. In this study, we re-evaluated the relation between CALHMI P86L polymorphism and risk for AD in a meta-analysis. Methods: This meta-analysis was performed using the PubMed, Science Direct, Scopus and Google Scholar databases up to June 2015 using the search terms "CALHM1" and "polymorphism or SNP or variant" in combination with "Alzheimer's disease". A meta-analysis with pooled odds ratios and 95% confidence intervals was carried out to assess the associations between P86L polymorphism and the risks for Alzheimer's disease under four genetic models with fixed or random effects models. Results: Sixteen studies (twenty-four subgroup studies involving 9795 cases and 15,335 controls) were included in our meta-analysis. Our meta-analysis results indicated that several genetic models of CALHM1 P86L polymorphism were significantly associated with increased risk for AD in overall and Caucasian populations. Conclusions: In conclusion, our comprehensive meta-analysis indicated that P86L polymorphism is significantly associated with an increased risk for AD. Our data suggest that CALHMI polymorphism may be potential biomarker in patients with AD. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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