LongevityMap Gene

Gene details

HGNC symbol: PON1
Aliases: ESA; PON; MVCD5
Common name: paraoxonase 1
Description: The enzyme encoded by this gene is an arylesterase that mainly hydrolyzes paroxon to produce p-nitrophenol. Paroxon is an organophosphorus anticholinesterase compound that is produced in vivo by oxidation of the insecticide parathion. Polymorphisms in this gene are a risk factor in coronary artery disease. The gene is found in a cluster of three related paraoxonase genes at 7q21.3. [provided by RefSeq, Oct 2008]
Cytogenetic Location: 7q21.3
UCSC Genome Browser: View 7q21.3 on the UCSC genome browser
OMIM: 168820
Ensembl: ENSG00000005421
UniProt/Swiss-Prot: PON1_HUMAN
Entrez Gene: 5444
UniGene: 370995
1000 Genomes: 1000 Genomes

Homologs in model organisms

Caenorhabditis elegans: poml-4
Caenorhabditis elegans: mec-6
Caenorhabditis elegans: poml-2
Caenorhabditis elegans: poml-3
Danio rerio: pon3.2
Danio rerio: pon3.2
Danio rerio: pon2
Danio rerio: pon1
Mus musculus: Pon1
Rattus norvegicus: Pon1

In other databases

GenAge human genes

This gene is present as PON1

CellAge

This gene is present as PON1

Studies (7)

Significant/Non-significant: 5/2

Study 1

Longevity Association

Population

Study Design

A Leucine (L allele) to Methionine (M allele) substitution at codon 55, and a Glutamine (A allele) to Arginine (B allele) substitution at codon 192 were examined in 579 people aged 20 to 65 years old, and in 308 centenarians

Conclusions

Significant differences between young people and centenarians were observed. The percentage of carriers of the B allele at codon 192 is higher in centenarians than in controls (0.539 vs 0.447), though this was due to an increase of people carrying M alleles at codon 55.

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Reference

Study 2

Longevity Association

Population

Study Design

Polymorphism at codon 192 (Gln/Arg) was examined in 256 healthy Caucasian men (69.8 +/- 4.0 years)

Conclusions

Gln homozygotes are more frequent in aging than Arg allele carriers

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Study 3

Longevity Association

Population

Italian and N. Irish

Study Design

PON1 55 (L/M) and 192 (Q/R) polymorphisms were studied in 308 Italian centenarians and 579 adult controls and 296 Irish octo/nonagenarians and 296 young controls

Conclusions

There was a significant difference in 192 genotypes in Italian centenarians compared to younger controls and a similar but non-significant trend between octo/nonagenarian and young subjects in Ireland. Distribution of the 55 (L/M) polymorphism frequencies were similar in both groups.

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Study 4

Longevity Association

Population

Italian (Sicily)

Study Design

The promoter T(-107)C and coding region Gln192Arg (Q192R) and Leu55Met (L55M) polymorphisms were examined in 100 healthy octogenarians and 200 adults

Conclusions

Octagenerians displayed significant higher levels of PON1 activity and had an higher percentage of (-107)CC compared with controls. No difference in the L55M and Q192R genotypes distribution was found in both groups.

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Study 5

Longevity Association

Population

Study Design

Two coding polymorphisms, 55M/L and 192Q/R, and a promoter variant, -107C/T, were studied in 1932 Danish individuals aged 47-93 years

Conclusions

A cross-sectional study comparing the genotype distribution of the three polymorphisms as well as the haplotype distribution in different age groups did not reveal any difference. However, a longitudinal follow-up study on survival in the same sample indicated that 192RR homozygotes have a poorer survival of coronary heart disease compared to QQ homozygotes.

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Reference

Study 6

Longevity Association: Non-significant
Population: Italian (Southern)
Study Design: A two-stage case-control study was performed to identify the association between longevity and variation of in homeostasis regulation pathway genes. 317 SNPs in 104 genes were analyzed in 78 cases (≥90 years, median age 98 years, 42 females) and 71 controls (<90 years, median age 67 years, 32 females) in stage 1. Then, 31 candidate SNPs identified in stage 1 (π markers = 0.1) were analyzed in an independent sample composed by 288 cases (≥90 years, median age 92 years, 163 females) and 554 controls (<90 years, median age 67 years, 277 females).
Conclusions: After adjustment for multiple testing, no significant association was identified between various SNPs and longevity.
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Study 7

Longevity Association: Non-significant
Population: Danish
Study Design: 38 genes (311 SNPs) belonging to pro-antioxidant pathways were investigated for the association with physical and cognitive performances in a Cohort of 1089 Danish nonagenarians. For each gene analyzed in the pro-antioxidant pathway, the influence on longitudinal survival was tested.
Conclusions: No gene found associated with a functional phenotype showed a corresponding association with survival in the whole cohort. NDUFS1, TXNRD1, SOD2 and UCP3 were found significantly associated with lifespan in the female cohort. No association with survival was reported in males for genes belonging to the pro-oxidant pathway here analyzed.
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