LongevityMap Gene

Gene details

HGNC symbol
IL6 
Aliases
CDF; HGF; HSF; BSF2; IL-6; BSF-2; IFNB2; IFN-beta-2 
Common name
interleukin 6 
Description
This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
Cytogenetic Location
7p15.3
UCSC Genome Browser
View 7p15.3 on the UCSC genome browser
OMIM
147620
Ensembl
ENSG00000136244
UniProt/Swiss-Prot
B4DNQ5_HUMAN
Entrez Gene
3569
UniGene
654458
1000 Genomes
1000 Genomes

Homologs in model organisms

Mus musculus
Il6
Rattus norvegicus
Il6

In other databases

GenAge human genes
  • This gene is present as IL6

Studies (17)

Significant/Non-significant: 5/12

Study 1

Longevity Association
Non-significant
Population
Irish (Northern)
Study Design
100 and 93 octogenarian and nonagenarian subjects + 182 control subjects (41% male, 59% female) were examined for -174 polymorphism
Conclusions
The frequency of GG homozygotes decreases with age by about 10% compared with young controls, though this is borderline significant. CC homozygotes have higher serum levels of IL-6 levels compared with GG.
Indentifier
-174C/G
Reference

    Study 2

    Longevity Association
    Non-significant
    Population
    Irish
    Study Design
    100 control samples (59% female and 41% male) and 93 aged consecutive samples (70% female, 30% male with an age range of 80-97 years) were analyzed for -174G/C SNP
    Conclusions
    No significant difference between centenarians and controls was observed
    Indentifier
    -174C/G
    Reference

      Study 3

      Longevity Association
      Non-significant
      Population
      Bulgarian
      Study Design
      -174G/C SNP was examined in 17 unrelated elderly (age 65-90 years; 6 males and 11 females), 23 family members (age 18-57 years; 9 males and 14 females, and a control group with 105 randomly selected, matched for geographical distribution healthy controls
      Conclusions
      GC genotype was higher in elders while GG genotype was lower in elders, though differences were not statistically significant after correcting for multiple testing
      Indentifier
      -174C/G
      Reference

        Study 4

        Longevity Association
        Non-significant
        Population
        Italian (Southern)
        Study Design
        -174 G/C promoter polymorphism was examined in a population of 81 centenarians compared with a control group of 122 middle-aged healthy subjects
        Conclusions
        No differences were found in allele and genotype frequencies between centenarians and controls
        Indentifier
        -174C/G
        Reference

          Study 5

          Longevity Association
          Significant
          Population
          Danish
          Study Design
          Three SNPs (-597G/A, -572G/C and -174G/C) and the AT-stretch polymorphism (-373(A)n(T)m) were examined in 1710 Danish subjects ranging in age from 47 to 100 years
          Conclusions
          A modest, but significant, increase in the frequency of -174GG homozygotes with age was observed. However, this increase is mainly followed by a concomitant decrease in GC heterozygotes rather than in CC homozygotes, as may be expected if the C allele is associated with decreased survival chance.
          Indentifier
          -174C/G
          Reference

            Study 6

            Longevity Association
            Non-significant
            Population
            Italian (Sardinia)
            Study Design
            112 (36 male, 76 female) centenarians, as well as 137 sixty-year-old controls were analyzed for -174G/C SNP
            Conclusions
            No significant difference between centenarians and controls was observed
            Indentifier
            -174C/G
            Reference

              Study 7

              Longevity Association
              Significant
              Population
              Finnish
              Study Design
              The promoter (-174G/C) SNP was examined in 285 nonagenarians (representing mortality between 90 and 95 years of age)
              Conclusions
              The frequency of allele G was higher in the survivors (n = 114) than in the non-survivors (n = 171)
              Indentifier
              -174C/G
              Reference

                Study 8

                Longevity Association
                Non-significant
                Population
                American (Caucasian)
                Study Design
                Genotypes for -174 G/C were studied in 2224 men and women aged 65 years or older at baseline
                Conclusions
                During 10 years of follow-up, a possible interaction between anti-inflammatory drugs, -174 C/C genotype, and longevity was found
                Indentifier
                -174C/G
                Reference

                  Study 9

                  Longevity Association
                  Non-significant
                  Population
                  Japanese
                  Study Design
                  -634 C/G SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100)
                  Conclusions
                  No association with longevity was found
                  Indentifier
                  -634C/G
                  Reference

                    Study 10

                    Longevity Association
                    Non-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
                    In a 11 years of follow-up study in the Danish, rs2069827 in IL6 was borderline significantly associated with survival from age 92 (P-corrected = 0.064). Investigation of the Dutch replication study supported an effect on late life survival.
                    Indentifier
                    rs2069827
                    Reference

                      Study 11

                      Longevity Association
                      Non-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
                      rs1800795 was not associated with longevity
                      Indentifier
                      rs1800795
                      Reference

                        Study 12

                        Longevity Association
                        Significant
                        Population
                        Turkish
                        Study Design
                        354 individuals (18 - 95 years, mean age 55.35 ± 19.16 y; 175 females (20–95 years, mean age 55.44 ± 19.15 years) and 179 males (18–92 years, mean age 55.27 ± 19.22 years) were classified into four age groups as 20–40, 41–60, 61–80, >80. Then, IL-6 and MT2A polymorphisms were genotyped for longevity association study.
                        Conclusions
                        A highly statistically significant association was detected for IL-6 genotype and allele frequencies in aging (p < 0.001). No significant difference was found between the two genders (p > 0.05). IL-6 −174 C+ carriers are more advantageous for longevity.
                        Indentifier
                        rs1800795
                        Reference

                          Study 13

                          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
                          rs1800795
                          Reference

                            Study 14

                            Longevity Association
                            Significant
                            Population
                            Danish
                            Study Design
                            IL6 (−597G/A, −572G/C and −174G/C) and the AT-stretch polymorphism (−373(A)n(T)m) were examined in 1710 Danish subjecta (47- 100y) to detect if a specific genotype or haplotype was associated with either longevity or increased mortality.
                            Conclusions
                            There was an almost complete allelic association between the −597G allele and the −174G allele. A modest, but significant, increase in the frequency of interleukin-6 −174GG homozygotes with age was observed. This genotype is advantageous for longevity.
                            Indentifier
                            rs1800795
                            Reference

                              Study 15

                              Longevity Association
                              Non-significant
                              Population
                              Danish
                              Study Design
                              IL6 (−597G/A, −572G/C and −174G/C) and the AT-stretch polymorphism (−373(A)n(T)m) were examined in 1710 Danish subjecta (47- 100y) to detect if a specific genotype or haplotype was associated with either longevity or increased mortality.
                              Conclusions
                              Four different −373(A)n(T)m alleles were detected in the Danish population; (A)8(T)12, (A)9(T)11, (A)10(T)10 and (A)10(T)11. The frequency of the (A)8(T)12 allele decreased slightly in the elderly group, yet not significantly (p>0.05). There was no difference in the −572G/C genotype distribution between age-groups.
                              Indentifier
                              Rs1800796
                              Reference

                                Study 16

                                Longevity Association
                                Significant
                                Population
                                Italian
                                Study Design
                                700 individuals (482 women and 218 men), ranging from 60 to 110 years of age including 323 centenarians were subdivided into three age-groups (60-80, 81-99 and over 99 years of age), and were assessed for -174 C/G locus variability
                                Conclusions
                                The proportion of homozygotes for the G allele decreases in centenarian males, but not in centenarian females. Among males, homozygotes for the G allele have higher IL-6 serum levels in comparison with carriers of the C allele.
                                Indentifier
                                -174C/G
                                Reference

                                  Study 17

                                  Longevity Association
                                  Non-significant
                                  Population
                                  Finnish
                                  Study Design
                                  250 (52 males and 198 females) nonagenarians and 400 healthy control group (18-60 years old) were examined for -174, +3953 and -511 SNPs
                                  Conclusions
                                  No significant differences relative to longevity were found
                                  Indentifier
                                  IL6
                                  Reference