%0 Journal Article %J J Alzheimers Dis %D 2018 %T Frequency of Cardiovascular Genetic Risk Factors in a Calabrian Population and Their Effects on Dementia. %A Maletta, Raffaele %A Smirne, Nicoletta %A Bernardi, Livia %A Anfossi, Maria %A Gallo, Maura %A Conidi, Maria Elena %A Colao, Rosanna %A Puccio, Gianfranco %A Curcio, Sabrina A M %A Laganà, Valentina %A Frangipane, Francesca %A Cupidi, Chiara %A Mirabelli, Maria %A Vasso, Franca %A Torchia, Giusi %A Muraca, Maria G %A Di Lorenzo, Raffaele %A Rose, Giuseppina %A Montesanto, Alberto %A Passarino, Giuseppe %A Bruni, Amalia C %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Apolipoprotein E4 %K Case-Control Studies %K Cholesterol Ester Transfer Proteins %K Cohort Studies %K Dementia, Vascular %K Female %K Frontotemporal Dementia %K Gene Frequency %K Humans %K Italy %K Male %K Middle Aged %K Polymorphism, Genetic %K Risk Factors %X

BACKGROUND: Several genetic variants playing a key role in cholesterol levels, blood pressure, and vascular dysfunction influence the risk of Alzheimer's disease (AD) and vascular dementia (VaD). The many meta-analysis studies carried out on large numbers of samples in different populations have not provided clear results to date, because a trans-ethnic shift of risk genotypes in different populations is often observed.

OBJECTIVES: To determine genotypes allele frequencies of the polymorphisms most frequently identified to be correlated with cardio-cerebrovascular disease and AD in a Southern Italy population and to investigate their possible association with dementia.

METHODS: The genotype and allele frequencies of 13 cardio-cerebrovascular risk polymorphisms were assessed and their possible association with dementia was investigated in a case-control study, including 221 consecutive unrelated subjects diagnosed with dementia (120 subjects affected by AD, 55 by frontotemporal dementia, and 33 by vascular dementia) and 218 matched controls of Calabrian origin.

RESULTS: Carriers of at least one APOEɛ4 allele resulted to be at higher risk of AD [OR(95% CI) = 2.721(1.477-5.011)] and VaD [OR(95% CI) = 6.205(2.356-16.342)] compared to non-carriers. Individuals with the IV genotype of the CETP polymorphism were more likely to have AD [OR(95% CI) = 2.427(1.364-4.319)] and VaD [OR(95% CI) = 3.649(1.455-9.152)] compared to subjects with the II-VV genotypes.

CONCLUSION: CETP I405V polymorphism is likely a risk factor for AD and VaD in our cohort, independent of APOEɛ4 status. Unmodifiable genetic risk factors should be taken into account to promote a healthy lifestyle to prevent dementia.

%B J Alzheimers Dis %V 61 %P 1179-1187 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29332048?dopt=Abstract %R 10.3233/JAD-170687 %0 Journal Article %J J Alzheimers Dis %D 2016 %T The Genetic Variability of UCP4 Affects the Individual Susceptibility to Late-Onset Alzheimer's Disease and Modifies the Disease's Risk in APOE-ɛ4 Carriers. %A Montesanto, Alberto %A Crocco, Paolina %A Anfossi, Maria %A Smirne, Nicoletta %A Puccio, Gianfranco %A Colao, Rosanna %A Maletta, Raffaele %A Passarino, Giuseppe %A Bruni, Amalia C %A Rose, Giuseppina %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Apolipoprotein E4 %K Female %K Genetic Association Studies %K Genotype %K Humans %K Male %K Mental Status Schedule %K Mitochondrial Uncoupling Proteins %K Neuroimaging %K Polymorphism, Single Nucleotide %X

Uncoupling proteins (UCPs) are a group of five mitochondrial inner membrane transporters with a tissue specific expression that uncouple biofuel oxidation from ATP synthesis and function as regulators of energy homeostasis and antioxidants. Previous data suggested that neuronal UCPs (UCP2, UCP4, and UCP5) can directly influence synaptic plasticity, neurotransmission, and neurodegenerative processes, and have a crucial role in the function and protection of the central nervous system. In fact, it has been observed that the expression of neuronal UCPs significantly decreases in Alzheimer's disease (AD) patients. Here we analyzed the variability of UCP2, -3, -4, and 5 genes in sporadic and familial cases (n = 465) of late-onset AD (LOAD) with respect to healthy controls (n = 442). We showed that a genetic variant in the human UCP4, rs9472817, not only significantly affects the individual susceptibility to LOAD, but also modulates the effect of APOE-ɛ4 on AD risk. In fact, rs9472817-C allele was significantly more frequent in both groups of patients with respect to the control group (p = 6.934*10-4 for familial and p = 1.033*10-3 for sporadic cases). In addition, gene-gene interaction analysis revealed that the effect of APOE-ɛ4 allele on LOAD risk was doubled in homozygote CC subjects; conversely, the risk conferred by the APOE-ɛ4 allele was annulled in subjects with two copies of the G allele. Our findings are further evidence that the efficiency in mitochondrial energy metabolism and oxidative stress are important factors in AD pathogenesis.

%B J Alzheimers Dis %V 51 %P 1265-74 %8 2016 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/26923023?dopt=Abstract %R 10.3233/JAD-150993