Linkage of human tumor necrosis factor-alpha to human osteoporosis by sib-pair analysis

N. Ota, Steven Hunt, T. Nakajima, T. Suzuki, T. Hosoi, H. Orimo, Y. Shirai, M. Emi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Osteoporosis as well as osteopenia are common human conditions considered to result from the interplay of multiple genetic and environmental factors. Twin and family studies have yielded strong correlation between measures of bone mass and a number of genetic factors. Certain genes (eg, cytokines such as interleukin-1, interleukin-6, or tumor necrosis factor-alpha) are capable of regulating metabolism, formation, and resorption of bone; all processes that determine bone mass. We tested 192 sib-pairs of adult Japanese women from 136 families for genetic linkage between osteoporosis and osteopenia phenotypes and allelic variants at the tumor necrosis factor-alpha (TNFA) locus, using a dinucleotide-repeat polymorphism located near the gene. The TNFA locus showed evidence for linkage to osteoporosis, with mean allele sharing of 0.478 (P = 0.30) in discordant pairs and 0.637 (P = 0.001) in concordant affected pairs. Linkage with osteopenia was also significant in concordant affected pairs (P = 0.017). Analyses limited to the post-menopausal women in our cohort showed similar or even stronger linkage for both phenotypes. The results provide evidence that genetic variations within the TNFA locus or adjacent genes affect regulation of mineral metabolism in bone and some of them confer risk for osteoporosis in adult women.

Original languageEnglish
Pages (from-to)260-264
Number of pages5
JournalGenes and Immunity
Volume1
Issue number4
Publication statusPublished - Apr 2000
Externally publishedYes

Fingerprint

Osteoporosis
Metabolic Bone Diseases
Tumor Necrosis Factor-alpha
Bone and Bones
Genes
Dinucleotide Repeats
Phenotype
Twin Studies
Genetic Linkage
Bone Resorption
Interleukin-1
Osteogenesis
Minerals
Interleukin-6
Alleles
Cytokines
human TNF protein

Keywords

  • Bone mineral density
  • Microsatellite polymorphism
  • Osteopenia
  • Osteoporosis
  • Sib-pair linkage
  • Tumor necrosis factor-alpha gene

ASJC Scopus subject areas

  • Genetics
  • Immunology
  • Genetics(clinical)

Cite this

Ota, N., Hunt, S., Nakajima, T., Suzuki, T., Hosoi, T., Orimo, H., ... Emi, M. (2000). Linkage of human tumor necrosis factor-alpha to human osteoporosis by sib-pair analysis. Genes and Immunity, 1(4), 260-264.

Linkage of human tumor necrosis factor-alpha to human osteoporosis by sib-pair analysis. / Ota, N.; Hunt, Steven; Nakajima, T.; Suzuki, T.; Hosoi, T.; Orimo, H.; Shirai, Y.; Emi, M.

In: Genes and Immunity, Vol. 1, No. 4, 04.2000, p. 260-264.

Research output: Contribution to journalArticle

Ota, N, Hunt, S, Nakajima, T, Suzuki, T, Hosoi, T, Orimo, H, Shirai, Y & Emi, M 2000, 'Linkage of human tumor necrosis factor-alpha to human osteoporosis by sib-pair analysis', Genes and Immunity, vol. 1, no. 4, pp. 260-264.
Ota N, Hunt S, Nakajima T, Suzuki T, Hosoi T, Orimo H et al. Linkage of human tumor necrosis factor-alpha to human osteoporosis by sib-pair analysis. Genes and Immunity. 2000 Apr;1(4):260-264.
Ota, N. ; Hunt, Steven ; Nakajima, T. ; Suzuki, T. ; Hosoi, T. ; Orimo, H. ; Shirai, Y. ; Emi, M. / Linkage of human tumor necrosis factor-alpha to human osteoporosis by sib-pair analysis. In: Genes and Immunity. 2000 ; Vol. 1, No. 4. pp. 260-264.
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