Genetic and environmental influences on IL-6 and TNF-alpha plasma levels in apparently healthy general population.
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-alpha 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-alpha 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-alpha 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-alpha, revealed small contribution of genetic factors (24.1 +/- 10.2%). The bivariate variance component analysis demonstrated that significant relationship between IL-6 and TNF-alpha was due to shared environment only (r(E)=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.
Pantsulaia
I
I
Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
Pantsulaia
Ia
Ia
Trofimov
Svetlana
S
Kobyliansky
Eugene
E
Livshits
Gregory
G
D000328:Adult; D000367:Age Factors; D000368:Aged; D001835:Body Weight; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D012016:Reference Values; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha