Genetic and environmental influences on IL-6 and TNF-α plasma levels in apparently healthy general population

Ia Pantsulaia, Svetlana Trofimov, Eugene Kobyliansky, Gregory Livshits*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Dysregulation of cytokines synthesis is thought to play a role in the development of a number of age-related conditions, such as rheumatoid arthritis, osteoporosis, atherosclerosis, and others, but observational studies have led to contradictory results. We investigated potential familial influences on the plasma levels of IL-6 and TNF-α in 91 nuclear and more complex pedigrees of Caucasian ethnic origin (N=401 individuals). The maximum likelihood based variance decomposition analysis showed significant positive correlation between circulating IL-6 and age in both genders. The magnitude of these correlations in our sample ranged from 0.22 in females to 0.28 in males (P<0.001). Significant association between TNF-α and IL-6 (r=0.28, r=0.43; P<0.001; respectively for men and women) was also observed. Likelihood ratio test clearly revealed that additive genetic effect for TNF-α was highly significant (P<0.001), and accounted over 80% of its variation, adjusted for IL-6 levels and age. In contrast, heritability estimate for IL-6 adjusted for age and TNF-α, revealed small contribution of genetic factors (24.1 ± 10.2%). The bivariate variance component analysis demonstrated that significant relationship between IL-6 and TNF-α was due to shared environment only (rE=0.760 ± 0.140). As evinced from our complex segregation analysis the nature of the genetic determinant of each of these two cytokines is quite complex and it is probably oligogenic.

Original languageEnglish
Pages (from-to)138-146
Number of pages9
JournalCytokine
Volume19
Issue number3
DOIs
StatePublished - 2002

Funding

FundersFunder number
Council for Higher Education‘s Planning and Budgeting Committee
Ministry of Foreign Affairs and Israel National Commission
United Nations Educational, Scientific and Cultural Organization
Ministry of Education
Iran National Science Foundation544/00–1
Iran National Science Foundation

    Keywords

    • Heritability
    • Interleukin-6
    • Model-fitting analysis
    • Pedigrees
    • Tumour necrosis factor-α

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