TY - JOUR
T1 - Genetic and environmental influences on IL-6 and TNF-α plasma levels in apparently healthy general population
AU - Pantsulaia, Ia
AU - Trofimov, Svetlana
AU - Kobyliansky, Eugene
AU - Livshits, Gregory
N1 - Funding Information:
This study was supported jointly by the Israel National Science Foundation (Grant # 544/00–1) and by a Postdoctoral Fellowship Grant (P.I.) kindly provided by UNESCO and Israel (the Ministry of Education, the Council for Higher Education‘s Planning and Budgeting Committee, the Ministry of Foreign Affairs and Israel National Commission for UNESCO).
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Heritability
KW - Interleukin-6
KW - Model-fitting analysis
KW - Pedigrees
KW - Tumour necrosis factor-α
UR - http://www.scopus.com/inward/record.url?scp=0036401434&partnerID=8YFLogxK
U2 - 10.1006/cyto.2002.1959
DO - 10.1006/cyto.2002.1959
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AN - SCOPUS:0036401434
SN - 1043-4666
VL - 19
SP - 138
EP - 146
JO - Cytokine
JF - Cytokine
IS - 3
ER -