The Study ofAPOA1,APOC3andAPOA4Variability in Healthy Ageing People Reveals Another Paradox in the Oldest Old Subjects

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Abstract
Summary: 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 theAPOA1,APOC3, andAPOA4gene 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), andAPOA4‐HincII‐RFLP (Asp127/Ser127) were analysed according to age and sex. A significant age‐related variation of theAPOA1gene pool was observed in males. An analysis of the allele average effect exerted byAPOA1‐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”.