The Contribution of Familial Resemblance to Variation in Circulatory Levels of Tissue Inhibitors of Metalloproteinases and Transforming Growth Factor-β1

I. Pantsulaia, S. Trofimov, L. Kalichman, E. Kobyliansky, G. Livshits

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

This study attempted to elucidate the genetic and environmental factors influencing interindividual variation of circulating TIMP-1, TIMP-2 and TGF-β1 and to clarify the relationship between the latter biochemical indices and hand osteoarthritis in an ethnically homogeneous sample. Plasma levels of each of the above biochemical indices were measured in 401 healthy individuals (aged 18-75 years) belonging to 90 nuclear and more complex families. Variance component analysis showed that a major part of the interindividual differences in TGF-β1, TIMP-1 and TIMP-2 levels was credibly attributable to genetic and familial factors. Adjusted for significant covariates, the putative genetic effects on the above three amounted to 0.40 ± 0.10, 0.47 ± 0.11 and 0.72 ± 0.10, respectively. Common environmental factors, shared by members of the same household, also contributed significantly (P < 0.01) to variation of each of the biochemical indices and explained between 27.6% (TIMP-2) and 38.7% (TGF-β1) of their variation. A bivariate analysis revealed a strong and highly significant correlation between TIMP-1 and TGF-β1 (r = 0.58 P < 0.001), which was due to common genetic and environmental sources (rG = 0.62 ± 0.09, rE = 0.31 ± 0.11, both P < 0.001). The analysis also detected modest but significant genetic correlation between TIMP-1 and TIMP-2 rG = 0.307 ± 0.108 P < 0.01). The present study evinces a strong genetic dependence for the plasma levels of both TIMPs and TGF-β1 and provides a basis for the further analysis of genetic variation affecting and regulating the circulatory concentrations of TIMPs and TGF-β1 in healthy humans.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalCalcified Tissue International
Volume74
Issue number1
DOIs
StatePublished - 1 Jan 2004
Externally publishedYes

Keywords

  • Genetic correlation
  • Heritability estimate
  • TGF-β1
  • TIMP-1
  • TIMP-2
  • Variance components

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Fingerprint

Dive into the research topics of 'The Contribution of Familial Resemblance to Variation in Circulatory Levels of Tissue Inhibitors of Metalloproteinases and Transforming Growth Factor-β1'. Together they form a unique fingerprint.

Cite this