The Study of APOA1, APOC3 and APOA4 Variability in Healthy Ageing People Reveals Another Paradox 
 in the Oldest Old Subjects

Abstract

SummaryThe 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 (Asp 127 /Ser 127 ) were analysed according to age and sex. A significant agerelated 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".

Development of a serum profile for healthy aging

“…It has been suggested as a biomarker of aging in Fisher 344 rats (Acuna-Castillo et al 2006). ApoA4 is a lipoprotein that has been implicated in Alzheimer's disease (Carter 2007) and aging (Garasto et al 2003). Gelsolin is a calcium-activated actin filament also linked to a number of pathological conditions such as cancer (Spinardi and Witke 2007).…”

Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity

“…In addition, AA genotype was associated with type II diabetes [17]. Despite the association between G allele and LDL serum level, this allele has higher frequency in healthy Italian centenarians [7].…”

“…Apolipoproteins are closely involved in lipid metabolism. APOA1/C3/A4/A5 gene cluster, located in 11q23, has been associated with familial combined hyperlipidemia [4,5] and with lipid plasma levels [6][7][8].…”

Association of the mitochondrial DNA haplogroup J with longevity is population specific

“…Details on the recruitment strategies are given elsewhere. 9 The DNA analyses to ascertain the J-haplogroup mutations are decribed in a previous report. 2 To figure out the age-related frequency trajectories of J haplogroup, a straight line y ¼ b 0 þ b 1 x was fitted to the relevant frequency data observed in five age classes (18 -40; 41 -55; 56 -70; 71 -85 and Z86 years), thus obtaining estimates b 0 and b 1 of b 0 and b 1 , respectively.…”