LongevityMap Gene

Gene details

HGNC symbol: TNF
Aliases: DIF; TNFA; TNFSF2; TNLG1F; TNF-alpha
Common name: tumor necrosis factor
Description: This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer. Knockout studies in mice also suggested the neuroprotective function of this cytokine. [provided by RefSeq, Jul 2008]
Cytogenetic Location: 6p21.33
UCSC Genome Browser: View 6p21.33 on the UCSC genome browser
OMIM: 191160
Ensembl: ENSG00000232810
UniProt/Swiss-Prot: Q5STB3_HUMAN
Entrez Gene: 7124
UniGene: 241570
1000 Genomes: 1000 Genomes

Homologs in model organisms

Danio rerio: tnfb
Danio rerio: tnfa
Mus musculus: Tnf
Rattus norvegicus: LOC103694380
Rattus norvegicus: Tnf

In other databases

GenAge human genes

This gene is present as TNF

Studies (11)

Significant/Non-significant: 3/8

Study 1

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 -308 SNP

Conclusions

No significant differences relative to longevity were found

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Reference

Study 2

Longevity Association

Non-significant

Population

Study Design

Promoter -308 G/A SNP was examined in 72 centenarian men, 102 centenarian women and healthy unrelated controls (115 men and 112 women, aged 22-60 years)

Conclusions

The genotypic frequencies 308G and 308A, suggested to be associated with low and high TNF alpha production respectively, were not significantly different between centenarians and controls

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Reference

Study 3

Longevity Association

Non-significant

Population

Irish (Belfast)

Study Design

100 control samples (59% female, 41% male with an age-range of 19-45 years old) and 93 aged samples (70% female, 30% male with an age-range of 80-97 years old) were examined for the -308A/G SNP

Conclusions

No age-related allele or genotype frequencies were observed

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Reference

Study 4

Longevity Association

Non-significant

Population

Study Design

Promoter -308 (G/A) 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 aged 25-53 years (40 male and 65 female)

Conclusions

No significant differences relative to longevity were found

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Reference

Study 5

Longevity Association

Non-significant

Population

Study Design

The -308 G/A SNP was examined in 122 centenarians, 174 octogenarians and 47 healthy volunteers aged 18 to 30

Conclusions

The distribution of TNF-308 genotypes was not different across the three different age groups, but the GA genotype was associated with decreased prevalence of dementia in centenarians. The few centenarians with AA carrier status had higher mortality risk and tended to show higher plasma levels of TNF-alpha.

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Reference

Study 6

Longevity Association

Population

Study Design

The frequency of the -308 polymorphism was analyzed in 71 healthy elders, aged 80 to 96 years (mean 86.2 years). The control samples were obtained from 99 young (from 21 - 54 years; mean 35.2 years) healthy individuals unrelated to elders were studied, age ranged from 80 to 96 years (mean 86.2 years).

Conclusions

The TNF2 allele was increased in the elder group when compared to young controls

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Reference

Study 7

Longevity Association

Non-significant

Population

Study Design

-1031 T/C SNP was evaluated with age or gender in 500 Japanese persons (mean age: 56.7 years old, range: 19-100)

Conclusions

Though not statistically significant, the -1031 T/C polymorphism may be associated with age

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Reference

Study 8

Longevity Association

Non-significant

Population

Study Design

IL-10 -1028 G/A and TNF-alpha-308 G/A were genotyped in 119 randomly selected elderly subjects (41 women and 78 men) with a mean age of 90.2 years and young control subjects of 118 (46 women and 72 men) with a mean age of 31.9 years

Conclusions

No significant differences were found in the genotype and allele frequencies of TNF-alpha gene variants between the two groups (P > 0.05). IL-10 genotype and allele frequencies were significantly associated with longevity in men (P < 0.05) but not in women (P < 0.05).

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Reference

Study 9

Longevity Association: Significant
Population: Italian (Central)
Study Design: Functional SNPs have been determined for 1071 unrelated healthy individuals (502 males and 569 females) from Central Italy, 18-106 years old, divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes. The categories for men were: individuals <66 years old, individuals 66-88 years old, and individuals > 88 years old. The categories for women were: individuals <73 years old, individuals 73-91 years old, and individuals > 91 years old.
Conclusions: When comparing all 3 age groups, both two-loci and three-loci interaction are significantly associated with life-expectancy in males. For females, a significant two-loci interaction occurs in females between ADA 22G>A (rs73598374) and TNF-a 238G>A (rs361525) only when comparing young and mid-aged individuals.
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Study 10

Longevity Association

Population

Study Design

The TNF(A/G)-308 was genotyped in 747 subjects (401 women, ages: 19–110 years) to study the association with longevity

Conclusions

TNF region was associated with life expectancy (P = 0.0027). Allele A of TNF(A/G)-308 had a detrimental effect on life expectancy, and this effect is specific to men.

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Reference

Study 11

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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