Genetic Deficiency of Plasma Lipoprotein-Associated Phospholipase A₂ (PLA2G7 V297F Null Mutation) and Risk of Alzheimer's Disease in Japan

Article type: Short Communication

Authors: Koshy, Beena^{a; 1} | Miyashita, Akinori^{b; 1} | St. Jean, Pamela^{a; 1} | Stirnadel, Heide^c | Kaise, Toshihiko^d | Rubio, Justin P.^a | Mooser, Vincent^a | Kuwano, Ryozo^b | Irizarry, Michael C.^{c; *}

Affiliations: [a] Genetics, GlaxoSmithKline, Research Triangle Park, NC, USA | [b] Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan | [c] WW Epidemiology, GlaxoSmithKline, Research Triangle Park, NC, USA | [d] Epidemiology, GlaxoSmithKline, Tokyo, Japan

Correspondence: [*] Correspondence to: Michael C. Irizarry, M.D., M.P.H., Director, WW Epidemiology, GlaxoSmithKline, 5 Moore Drive, 17.2123, Research Triangle Park, North Carolina 27709, USA. Tel.: +1 919 483 7701; Fax: +1 919 315 4947; E-mail: [email protected].

Note: [1] Equal contribution.

Note: [] Handling Associate Editor: Estrella Gómez-Tortosa

Abstract: High plasma lipoprotein phospholipase A2 activity (Lp-PLA2) is reported to be a risk factor for dementia. A loss of function polymorphism in the Lp-PLA2 gene – PLA2G7 V279F – is found almost exclusively in Asians. In 1,952 subjects with late-onset AD and 2,079 non-demented controls recruited from Japan, the PLA2G7 null allele was not associated with risk or age at onset of AD: logistic regression OR 0.98 (95% CI 0.86–1.12, p = 0.81) per additional null allele, adjusted for age/age at onset, gender, and APOE ε4. Genetic deficiency of Lp-PLA2 activity is not associated with a reduced risk of AD in the Japanese population.

Keywords: Alzheimer's disease, apolipoprotein E, genetic association study, lipoprotein-associated phospholipase A2, Mendelian randomization

DOI: 10.3233/JAD-2010-100513

Journal: Journal of Alzheimer's Disease, vol. 21, no. 3, pp. 775-780, 2010