Key result
APOA1 P allele paradoxically links to higher LDL-cholesterol yet greater longevity in elderly males.
Why the study?
Polymorphisms of APOA1, APOC3, and APOA4 genes have been extensively studied in lipoprotein disorders and cardiovascular diseases but are poorly investigated in healthy ageing populations.
Cross-Sectional (n=800)
APOA1 P allele links to higher LDL yet centenarian enrichment in males; hypothesis-generating and should not change practice.
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".
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Garasto et al. (2003) conducted a cross-sectional in Healthy ageing (n=800). APOA1-MspI-RFLP A/P alleles vs. APOA1-MspI-RFLP A allele was evaluated on Allele frequency in the oldest old subjects and average effect on serum LDL-cholesterol. The APOA1-MspI-RFLP P allele significantly increased serum LDL-cholesterol in 46-80 year old males and was unexpectedly over-represented in the oldest old subjects, revealing a genetic paradox in centenarians.
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