LongevityMap Gene

Gene details

HGNC symbol: IGF1R
Aliases: IGFR; CD221; IGFIR; JTK13
Common name: insulin like growth factor 1 receptor
Description: This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]
Cytogenetic Location: 15q26.3
UCSC Genome Browser: View 15q26.3 on the UCSC genome browser
OMIM: 147370
Ensembl: ENSG00000140443
UniProt/Swiss-Prot: C9J5X1_HUMAN
Entrez Gene: 3480
UniGene: 643120
1000 Genomes: 1000 Genomes

Homologs in model organisms

Caenorhabditis elegans: daf-2
Danio rerio: igf1ra
Danio rerio: igf1rb
Drosophila melanogaster: InR
Mus musculus: Igf1r
Rattus norvegicus: Igf1r

In other databases

GenAge model organism genes

A homolog of this gene for Caenorhabditis elegans is present as daf-2
A homolog of this gene for Mus musculus is present as Igf1r
A homolog of this gene for Drosophila melanogaster is present as InR

GenAge human genes

This gene is present as IGF1R

GenDR gene manipulations

A homolog of this gene for Drosophila melanogaster is present as InR
A homolog of this gene for Caenorhabditis elegans is present as daf-2

Studies (6)

Significant/Non-significant: 4/2

Study 1

Longevity Association: Significant
Population: Italian
Study Design: Two polymorphisms were studied for effects on survival in 668 individuals aged 70-105.5 years and followed for 7 years
Conclusions: Male carriers of A/A genotype in rs2229765 lived longed
Indentifier

Study 2

Longevity Association

Population

Study Design

The G/A, codon 1013 polymorphism was examined in healthy people 17-85 yr of age (n= 278; mean age, 54.8; 76 males and 202 females) and in healthy people 86-109 yr of age (n= 218; mean age, 98.0; 56 males and 162 females)

Conclusions

The analysis revealed lower free IGF-I plasma levels in IGF1R A subjects (AG and AA genotypes) than in A- (GG genotype) subjects. A subjects were more represented among long-lived people than in young people.

Indentifier

Reference

Study 3

Longevity Association

Population

Ashkenazi Jewish

Study Design

Genetic variation in IGF1 and IGF1R were examined in a cohort of Ashkenazi Jewish centenarians (286 females and 98 males, average age 97.7 years), their offspring (114 females and 174 males, mean age 67.8 years), and offspring-matched controls (n = 312, mean age 79.5 years)

Conclusions

There was an overrepresentation of two nonsynonymous mutations in the IGF1R gene among centenarians relative to controls. These are also associated with high serum IGFI levels and reduced activity of the IGFIR as measured in transformed lymphocytes.

Indentifier

Reference

Study 4

Longevity Association: Non-significant
Population: American (Caucasian)
Study Design: 291 SNPs in 30 genes in the insulin/IGF1 signaling pathway were evaluated in 293 long-lived cases and 603 average-lifespan controls (all female), then replicated the candidate genes in two independent cohorts: 279 cases (47% male vs 797 controls(52.6% male) and 383 cases (25.2% male) vs 363 controls (42.7 % male)
Conclusions: Apart SNPs in FOXO3A and AKT1, no associations with longevity were significant after correcting for multiple testing, though SNPs in 7 other genes (FOXO1A, GHR, GHRHR, IGF1R, IGFBP3, IGFBP4, and PTEN) had suggestive significance
Indentifier

Study 5

Longevity Association: Significant
Population: Italian
Study Design: 722 unrelated subjects (401 women and 321 men, mean age, 62.83±25.30 years; 514 subjects aged <85y, mean age = 49 ± 16 year, and 208 individuals aged from 86 y to 104 y, mean age=96 ± 4) were analyzed to assess the impact of specific IRS-2, IGF1R and UCP2 gene variants with longevity
Conclusions: A IGF1R/Asp-IRS2/Val-UCP2 allele combination was associated with an increased probability to reach extreme old age (OD = 3.185 95% CI, 1.63–6.19; p < 0.0006)
Indentifier

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.
Indentifier