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

CellAge

This gene is present as IL6

Studies (17)

Significant/Non-significant: 5/12

Study 1

Longevity Association

Population

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.

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Reference

Study 2

Longevity Association

Non-significant

Population

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

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Reference

Study 3

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.

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Reference

Study 4

Longevity Association

Non-significant

Population

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

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Reference

Study 5

Longevity Association

Non-significant

Population

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

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Reference

Study 6

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

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Reference

Study 7

Longevity Association

Population

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.

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Study 8

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

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Reference

Study 9

Longevity Association

Population

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)

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Reference

Study 10

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

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Reference

Study 11

Longevity Association

Non-significant

Population

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

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Reference

Study 12

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

Study 13

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

Study 14

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

Study 15

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

Study 16

Longevity Association

Non-significant

Population

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.

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Reference

Study 17

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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