Published on Jan. 1, 2011 in J Alzheimers Dis volume 23(3).
PubMed ID: 21098976
The FTO gene has been shown to have a small but robust effect on body mass index(BMI) and to increase the risk for diabetes. Both high BMI and diabetes are vascularrisk factors that might play a role in the development of Alzheimer's disease (AD)and dementia. Thus, our aim was to explore the impact of FTO on AD and dementiarisk. Nine years of follow-up data was gathered from the Kungsholmen project, aprospective population-based study on 1,003 persons without dementia. Cox-regressionmodels were used to assess the relative risks of developing AD and dementia(DSM-III-R criteria) according to FTO genotypes (rs9939609), taking into accountAPOE, physical inactivity, BMI, diabetes, and cardiovascular disease (CVD). Comparedto carriers of the FTO TT-genotype, AA-carriers had a higher risk for AD (RR 1.58,95% CI: 1.11-2.24) and for dementia (RR 1.48, 95% CI: 1.09-2.02) after adjustmentfor age, gender, education, and APOE genotype. This effect remained after additionaladjustment for physical inactivity, BMI, diabetes, and CVD. An interaction betweenFTO and APOE was found, with increased risk for dementia for those carrying both FTOAA and APOE ϵ4. Importantly, the effect of the AA-genotype on dementia/AD risk seemsto act mostly through the interaction with APOE ϵ4. Our findings suggest that theFTO AA-genotype increases the risk for dementia, and in particular AD, independentlyof physical inactivity, BMI, diabetes, and CVD measured at baseline. Our results arein line with the recently reported association between FTO and reduced brain volumein cognitively healthy subjects.