APOA4
Apolipoprotein A-IV precursor (Apo-AIV) (ApoA-IV) (Apolipoprotein A4)
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In this study we explored the association between aging-related phenotypes previously reported to predict survival in old age and variation in 77 genes from the DNA repair pathway, 32 genes from the growth hormone 1/ insulin-like growth factor 1/insulin (GH/IGF-1/INS) signalling pathway and 16 additional genes repeatedly considered as candidates for human longevity: APOE, APOA4, APOC3, ACE, CETP, HFE, IL6, [[IL6R]], MTHFR, TGFB1, SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. Altogether, 1,049 single nucleotide polymorphisms (SNPs) were genotyped in 1,088 oldest-old (age 92-93 years) Danes and analysed with phenotype data on physical functioning (hand grip strength), cognitive functioning (mini mental state examination and a cognitive composite score), activity of daily living and self-rated health. Five SNPs showed association to one of the phenotypes; however, none of these SNPs were associated with a change in the relevant phenotype over time (7 years of follow-up) and none of the SNPs could be confirmed in a replication sample of 1,281 oldest-old Danes (age 94-100). Hence, our study does not support association between common variation in the investigated longevity candidate genes and aging-related phenotypes consistently shown to predict survival. It is possible that larger sample sizes are needed to robustly reveal associations with small effect sizes.
MeSH Terms
- Activities of Daily Living
- Aged, 80 and over
- Aging
- Cognition
- Denmark
- Female
- Genotype
- Hand Strength
- Humans
- Linear Models
- Longevity
- Male
- Phenotype
- Polymorphism, Single Nucleotide
- Signal Transduction
- Surveys and Questionnaires
Keywords
- Association study
- Human aging
- Oldest-old
- Single nucleotide polymorphisms
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".
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aged
- Aging
- Apolipoprotein A-I
- Apolipoprotein C-III
- Apolipoproteins A
- Apolipoproteins C
- Child
- Chromosomes, Human, Pair 11
- Cross-Sectional Studies
- DNA
- Female
- Gene Frequency
- Genotype
- Humans
- Lipids
- Male
- Middle Aged
- Polymorphism, Genetic
- Sex Factors