👤 Raffaele Maletta

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. 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. 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. 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. 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. Show less

The genes coding for apolipoprotein A1 (APOA1), apolipoprotein C3 (APOC3) and apolipoprotein A4 (APOA4) are tandemly organised within a short region on chromosome 11q23-q24. Polymorphisms of these genes have been extensively investigated in lipoprotein disorders and cardiovascular diseases, but poorly investigated in healthy ageing. The aim of this study was to describe possible modifications of the APOA1, APOC3, and APOA4 gene pool by cross-sectional studies carried out in a healthy ageing population whose ages ranged from 18 to 109 years (800 subjects, 327 males and 473 females, free of clinically manifested disease, and with emato-chemical parameters in the norm). APOA1-MspI-RFLP (-75 nt from the transcription starting site), APOC3-SstI-RFLP (3'UTR, 3238 nt), and APOA4-HincII-RFLP (Asp127/Ser127) were analysed according to age and sex. A significant age-related variation of the APOA1 gene pool was observed in males. An analysis of the allele average effect exerted by APOA1-MspI-RFLP A/P alleles (Absence/Presence of the restriction site) on lipidemic parameters in 46-80 year old males showed that allele A decreased, while allele P significantly increased, serum LDL-cholesterol. Unexpectedly, the P allele was over-represented in the group of the oldest old subjects, thus giving evidence of another "genetic paradox of centenarians". Show less