LongevityMap Gene

Gene details

HGNC symbol: WRN
Aliases: RECQ3; RECQL2; RECQL3
Common name: Werner syndrome RecQ like helicase
Description: This gene encodes a member of the RecQ subfamily and the DEAH (Asp-Glu-Ala-His) subfamily of DNA and RNA helicases. DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination, and repair. This protein contains a nuclear localization signal in the C-terminus and shows a predominant nucleolar localization. It possesses an intrinsic 3' to 5' DNA helicase activity, and is also a 3' to 5' exonuclease. Based on interactions between this protein and Ku70/80 heterodimer in DNA end processing, this protein may be involved in the repair of double strand DNA breaks. Defects in this gene are the cause of Werner syndrome, an autosomal recessive disorder characterized by premature aging. [provided by RefSeq, Jul 2008]
Cytogenetic Location: 8p12
UCSC Genome Browser: View 8p12 on the UCSC genome browser
OMIM: 604611
Ensembl: ENSG00000165392
UniProt/Swiss-Prot: Q59F09_HUMAN
Entrez Gene: 7486
UniGene: 632050
1000 Genomes: 1000 Genomes

Homologs in model organisms

Caenorhabditis elegans: wrn-1
Danio rerio: wrn
Mus musculus: Wrn
Rattus norvegicus: Wrn
Saccharomyces cerevisiae: SGS1

In other databases

GenAge model organism genes

A homolog of this gene for Saccharomyces cerevisiae is present as SGS1

GenAge human genes

This gene is present as WRN

CellAge

This gene is present as WRN

Studies (6)

Significant/Non-significant: 2/4

Study 1

Longevity Association

Non-significant

Population

Finnish, American, Mexican and Japanese

Study Design

The 1367 Cys/Arg polymorphism was examined during aging in 175 Finnish centenarians and 178 newborns, 169 Mexican newborns, 23 North American adults and 198 Japanese adults

Conclusions

When newborns and centenarians were compared within the Finnish population no differences were observed in the proportions of 1367 Cys/Arg across age groups. The frequency of the 1367 Arg allele, thought to be protective against myocardial infarction in a Japanese population, was approximately three times higher in the North American and Finnish adult populations.

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Reference

Study 2

Longevity Association: Significant
Population: Danish
Study Design: Alleles in candidate pathways (GH/IGF1 signaling, DNA damage signaling and repair and pro/antioxidants) were investigated for association with longevity in 1089 oldest-old (age 92-93) and 736 middle-aged Danes
Conclusions: Eleven SNPs (in GSR, KL, GHRHR, INS, GHSR, IGF2R, RAD52, WRN, RAD23B, POLB and NTLH1) were associated with longevity after correction for multiple hypothesis testing. No replications were observed in German and Dutch populations.
Indentifier

Study 3

Longevity Association

Non-significant

Population

Finnish and Mexican

Study Design

Population studies of the 1074Leu/Phe and 1367Cys/Arg polymorphisms were undertaken to evaluate the role of WRN in atherogenesis

Conclusions

Frequencies of the 1074Leu/Phe polymorphisms revealed an age-dependent decline of 1074Phe/Phe genotype. There was a tendency for the 1074Phe allele to be associated with coronary stenosis in a gene dose-dependent manner. The 1367Arg/Arg genotype predicted a lower degree of coronary artery occlusion, when compared to the 1367Cys/Cys or 1367Cys/Arg genotypes. However, these tendencies did not achieve statistical significance.

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Reference

Study 4

Longevity Association

Non-significant

Population

Study Design

The i1-C/T, L1074F and C1367R polymorphisms were examined in 1245 participants aged 85 years and older

Conclusions

The polymorphisms were not found to influence aging-trajectories or survival

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Reference

Study 5

Longevity Association: Significant
Population: American (Caucasian)
Study Design: Genome-wide association study in 801 centenarians and 914 healthy controls
Conclusions: 281 SNPs were found to discriminate between cases and controls
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Study 6

Longevity Association: Non-significant
Population: Danish
Study Design: 592 SNPs from 77 genes involved in nine sub-processes were analyzed in 1089 long-lived and 736 middle-aged Danes. Then, a replicated study was carried out in a German cohort.
Conclusions: The results did not remain significant after correction. The findings drawn from the Danish cohort were not replicated in German samples.
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