LongevityMap Gene

Gene details

HGNC symbol
APOE 
Aliases
AD2; LPG; APO-E; ApoE4; LDLCQ5 
Common name
apolipoprotein E 
Description
The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]
Cytogenetic Location
19q13.32
UCSC Genome Browser
View 19q13.32 on the UCSC genome browser
OMIM
107741
Ensembl
ENSG00000130203
UniProt/Swiss-Prot
A0A0S2Z3D5_HUMAN
Entrez Gene
348
UniGene
654439
1000 Genomes
1000 Genomes

Homologs in model organisms

Danio rerio
apoea
Mus musculus
Apoe
Rattus norvegicus
Apoe

In other databases

GenAge model organism genes
  • A homolog of this gene for Mus musculus is present as Apoe
GenAge human genes
  • This gene is present as APOE

Studies (26)

Significant/Non-significant: 20/6

Study 1

Longevity Association
Significant
Population
Swedish
Study Design
Isoforms were examined in 407 healthy Swedish individuals, 244 men and 163 women, ages 17 to 86 years
Conclusions
The E4 frequency decreased with increasing age and was significantly lower in individuals > 60 years of age
Indentifier
E2/E3/E4
Reference

    Study 2

    Longevity Association
    Non-significant
    Population
    Korean
    Study Design
    Common polymorphism was examined in 103 centenarians (13 men and 90 women, mean age 102.4 +/- 2.6 years) and in 6435 adults (5008 men and 1427 women) of mean age 50.7 +/- 7.9 years
    Conclusions
    The frequencies of genotypes and alleles of the centenarians were not significantly different from those of the control groups. The frequency of the E4 allele, however, was significantly higher in centenarians with dementia than in centenarians without definitive dementia.
    Indentifier
    E2/E3/E4
    Reference

      Study 3

      Longevity Association
      Non-significant
      Population
      Italian
      Study Design
      APOE common polymorphism (E2, E3, and E4) was examined in a sample of 228 healthy Italian subjects (124 men and 104 women) aged 18-93
      Conclusions
      The frequency of E4 decreased with age and was not found in subjects aged 75 and older
      Indentifier
      E2/E3/E4
      Reference

        Study 4

        Longevity Association
        Significant
        Population
        Russian (Novosibirsk)
        Study Design
        Common polymorphism was examined in 97 elderly subjects and control group aged 25-64
        Conclusions
        In men aged 83 years and older the frequency of the E3/E4 genotype was lower and that of the E2/E3 genotype was higher. In subjects of senile age and long-livers of both sexes genotype E4/E4 was not found.
        Indentifier
        E2/E3/E4
        Reference

          Study 5

          Longevity Association
          Non-significant
          Population
          English (Cambridge)
          Study Design
          Common polymorphism was examined in 182 women and 100 men aged > 84 years and in 100 boys and 100 girls younger than 17 years
          Conclusions
          Difference between genotypes in the elderly women and the young sample was observed. However, this did not retain significance when the genotype frequencies of the young sample were adjusted to values expected from the allele frequencies on the basis of Hardy-Weinberg equilibrium and compared to observed genotypes in elderly men and women.
          Indentifier
          E2/E3/E4
          Reference

            Study 6

            Longevity Association
            Non-significant
            Population
            Ashkenazi Jewish (Jerusalem)
            Study Design
            Common polymorphism was examined in 224 older (75 years) Jewish Jerusalem residents of Ashkenazi ethnicity (150 males and 74 females) and in a group of 441 younger subjects (22 years)
            Conclusions
            Ashkenazi older subjects were characterized by an increased percentage of the E2 allele and a decreased percentage of the E4 allele, though this was not significant after correcting for multiple testing
            Indentifier
            E2/E3/E4
            Reference

              Study 7

              Longevity Association
              Significant
              Population
              Chinese (Uighur in Xinjiang)
              Study Design
              Common polymorphism was examined in centenarians (n=42), 90-year-old people (n=102), 65-70-year-old people (n=70) and controls(n=53).
              Conclusions
              The frequencies of genotype E3/4 and E4, E3 alleles in the centenarian group were significantly lower than those in controls, whereas the frequencies of genotype E2/3 and E2 allele in the centenarian group were significantly higher than those in controls.
              Indentifier
              E2/E3/E4
              Reference

                Study 8

                Longevity Association
                Significant
                Population
                Italian (Southern)
                Study Design
                The association of sex and age with the occurrence of APOE genotypes in healthy aging and longevity in 1344 healthy individuals and 64 centenarians was examined
                Conclusions
                A higher E2 frequency was observed in men aged 60-90 years and in centenarians
                Indentifier
                E2/E3/E4
                Reference

                  Study 9

                  Longevity Association
                  Non-significant
                  Population
                  Columbian
                  Study Design
                  Polymorphisms were studied in a sample of 538 Colombian subjects (aged 18-106 years)
                  Conclusions
                  There were no differences between young and old subjects
                  Indentifier
                  APOE
                  Reference

                    Study 10

                    Longevity Association
                    Significant
                    Population
                    Greek
                    Study Design
                    The prevalence of genotypes in 80 healthy aged individuals (>80 years) and 391 adults (median age 43 years) was examined
                    Conclusions
                    Genotypes were comparable in both groups with the exception of E3/3 and E3/4, which were significantly higher and lower, respectively, in aged individuals. The epsilon2 and epsilon3 allele frequencies were not different between the groups. The epsilon4 allele was significantly less frequent in aged individuals compared to controls.
                    Indentifier
                    E2/E3/E4
                    Reference

                      Study 11

                      Longevity Association
                      Significant
                      Population
                      American (Georgia and Louisiana populations from African and European origin)
                      Study Design
                      Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity in the Georgia Centenarian Study (n=650) and Louisiana Healthy Aging Study (n=869)
                      Conclusions
                      APOE was associated with longevity
                      Indentifier
                      APOE
                      Reference

                        Study 12

                        Longevity Association
                        Significant
                        Population
                        Italian
                        Study Design
                        Genome-wide association study on 410 long-living individuals (age range, 90–109 years) and 553 young control individuals (age range, 18–48 years) using 318,237 SNPs. An independent population with 116 long-lived individuals and 160 controls was used for replication purposes.
                        Conclusions
                        rs429358 (APOE) was associated with longevity in the replication population
                        Indentifier
                        rs429358
                        Reference

                          Study 13

                          Longevity Association
                          Significant
                          Population
                          Irish (Belfast)
                          Study Design
                          APOE genotypes were assessed in 114 nonagenarians and 2071 younger controls (30-65 years)
                          Conclusions
                          The E4 allele was reduced in the nonagenarian group (X(2)=11.1; P=0.0006), the E3 unchanged and E2 frequency was increased (X(2)=4.0; P=0.047). Longevity is negatively associated with the E4 allele and may be associated with carriage of E2.
                          Indentifier
                          E2/E3/E4
                          Reference

                            Study 14

                            Longevity Association
                            Significant
                            Population
                            Chinese (Han)
                            Study Design
                            the relationship between APOE and longevity was analyzed among 1562 Han Chinese (ages ranged from 20-108 years, 246 female and 1316 male)
                            Conclusions
                            The allele frequency of APOE*4 in the very old age group (> or = 85 years) was significantly different from that in the youth (20-39 years), middle (40-59 years) and old (60-84 years) age group (2.5% vs 8.4, 7.9 or 7.6%; P < 0.05), respectively
                            Indentifier
                            E2/E3/E4
                            Reference

                              Study 15

                              Longevity Association
                              Significant
                              Population
                              American (Georgia and Louisiana populations from African and European origin)
                              Study Design
                              Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity in the Georgia Centenarian Study (n=650) and Louisiana Healthy Aging Study (n=869)
                              Conclusions
                              An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population.
                              Indentifier
                              APOE
                              Reference

                                Study 16

                                Longevity Association
                                Significant
                                Population
                                Danish
                                Study Design
                                The effect of the APOE alleles on mortality was studied in 2,262 persons aged 92–93 years
                                Conclusions
                                APOE ε4 carriers had a 22% increased mortality risk, but there was no protective effect of the APOE ε2 allele on mortality
                                Indentifier
                                rs429358
                                Reference

                                  Study 17

                                  Longevity Association
                                  Significant
                                  Population
                                  Dutch
                                  Study Design
                                  Genome-wide association study in 403 unrelated nonagenarians from long-living families and 1670 younger controls. Strongest candidates were then investigated in a meta-analysis of 4149 nonagenarian cases and 7582 younger controls.
                                  Conclusions
                                  No SNP reached significance in the GWAS but 62 SNPs had an indicative association with survival into old age. Of these 62 SNPs then studied in the meta-analysis, only one was significant: rs2075650 located in TOMM40 and close to APOE. This association may be due to linkage disequilibrium with rs429358 and rs7412 in APOE; both rs429358 and rs7412 were associated with longevity in the meta-analysis.
                                  Indentifier
                                  rs429358
                                  Reference

                                    Study 18

                                    Longevity Association
                                    Significant
                                    Population
                                    Danish, German, Dutch
                                    Study Design
                                    102 SNPs from 16 longevity candidate genes were examined in Danish. 1089 individuals (ages 92.2-93.8, mean age 93.2, 71.3 female) and 736 middle-aged controls (46-55 y, mean age 50.6, 49.6% female) were involved in this case-control study. Then the results were replicated in a German cohort of 1613 individuals (95-110 y, 73.2% female) and 1104 middle-aged controls (mean age 67.2, SD 4.07, 74.3% female). A 11 years study was introduced in Danish cohort to identify the SNPs associated with longevity, then the results were verified in Dutch longitudinal cohort.
                                    Conclusions
                                    The minor allele frequency of rs769449 in APOE was significantly decreased in the oldest-old. Haplotype case–control comparisons identified an haplotype with rs405509, rs440446 and rs769449 associated with longevity. Gene-based analysis confirmed the significant association of variations in APOE with longevity. The association of rs769449 was confirmed in the German population.
                                    Indentifier
                                    rs405509
                                    Reference

                                      Study 19

                                      Longevity Association
                                      Significant
                                      Population
                                      European and American (Caucasian)
                                      Study Design
                                      The allelic distribution of APOE isoforms E2, E3, and E4 were assessed among 10,623 participants
                                      Conclusions
                                      APOE alleles were associated with human longevity. There was a significant decrease in the frequency of E4 with increasing age (P = 0.0001), as well as a significantly increased frequency of E3 (P = 0.001). E2 showed little variation with age.
                                      Indentifier
                                      rs429358
                                      Reference

                                        Study 20

                                        Longevity Association
                                        Significant
                                        Population
                                        Finnish
                                        Study Design
                                        The common polymorphism of apolipoprotein E (E2, E3, and E4) was examined in 179 Finnish centenarians
                                        Conclusions
                                        The frequency of the E2 allele was higher and that of the E4 allele lower in the centenarians
                                        Indentifier
                                        E2/E3/E4
                                        Reference

                                          Study 21

                                          Longevity Association
                                          Significant
                                          Population
                                          Finnish
                                          Study Design
                                          Common polymorphism was examined in 179 persons (28 men and 151 women) aged 100 years and older
                                          Conclusions
                                          The percentages of E2-allele carriers increased with age, particularly in women. The percentage of carriers of the E4 allele was lower than expected.
                                          Indentifier
                                          E2/E3/E4
                                          Reference

                                            Study 22

                                            Longevity Association
                                            Significant
                                            Population
                                            French
                                            Study Design
                                            Common polymorphism was examined in centenarians (n = 338) and in adults aged 20-70 years
                                            Conclusions
                                            E4 allele was significantly less frequent in centenarians than in controls, while the frequency of the E2 allele was significantly increased
                                            Indentifier
                                            E2/E3/E4
                                            Reference

                                              Study 23

                                              Longevity Association
                                              Significant
                                              Population
                                              French
                                              Study Design
                                              Common polymorphism (E2, E3, and E4) was examined in 560 centenarians and 560 adult controls
                                              Conclusions
                                              Significant differences were observed between centenarians and controls for allelic and genotypic frequencies. The E4E4 genotype was under-represented in centenarians compared to controls. Centenarians carrying at least one E2 allele or homozygous for E3 were more frequent than controls.
                                              Indentifier
                                              E2/E3/E4
                                              Reference

                                                Study 24

                                                Longevity Association
                                                Significant
                                                Population
                                                Chinese (Uighur in Xinjiang)
                                                Study Design
                                                Common polymorphism (E2, E3, and E4) was studied in 164 subjects including 35 persons aged 90 years or older, 71 men aged 20-35 and 54 men with myocardial infarction
                                                Conclusions
                                                There was a statistically significant difference in the E4 allele frequencies among the three groups with the older group showing a lower E4 allele frequency
                                                Indentifier
                                                E2/E3/E4
                                                Reference

                                                  Study 25

                                                  Longevity Association
                                                  Non-significant
                                                  Population
                                                  Brazilian
                                                  Study Design
                                                  Common polymorphism was examined in 70 elderly patients aged 80 years or more
                                                  Conclusions
                                                  No association was observed between the genotypes and longevity, though individuals with the E3E4 genotype had a mean age greater than those with the E3E3 genotype.
                                                  Indentifier
                                                  E2/E3/E4
                                                  Reference

                                                    Study 26

                                                    Longevity Association
                                                    Significant
                                                    Population
                                                    Finnish
                                                    Study Design
                                                    The common polymorphism of apolipoprotein E (E2, E3, and E4) was examined in Finnish nonagenarians
                                                    Conclusions
                                                    The frequency of the E4 allele was lower in the nonagenarians than in the middle-aged and young adults
                                                    Indentifier
                                                    E2/E3/E4
                                                    Reference