The age-dependency of genetic and environmental influences on serum cytokine levels: A twin study

Previous epidemiologic studies have evaluated the use of immunological markers as possible tools for measuring ageing and predicting age-related pathology. The importance of both genetic and environmental influences in regulation of these markers has been emphasized. In order to further evaluate this relationship, the present study aims to investigate the relative influence of genetic and environmental factors on four key cytokines involved in the human immune response (Interleukin (IL)-1b, IL-6, IL-10 and Tumor Necrosis Factor (TNF)-a). In addition, the role of age as a possible moderator on these influences was evaluated. Methods: The study was conducted in 1603 females from the Twins UK registry, with mean age ±SD of 60.4 ± 12.2 years, including 863 monozygotic twins (385 pairs and 93 singletons) and 740 dizygotic twins (321 pairs and 98 singletons). Heritability was estimated using structural equation modeling. The role of age as a moderator was evaluated using gene-age interaction models. Results: Heritabilities were moderate for IL-1b (range: 0.27–0.32) and IL-10 (0.30) and low for IL-6 (range: 0.15–0.16) and TNF-a (range: 0.17–0.23). For IL-1b, heritability declines with age due to an increase in unique environmental factors. For TNF-a, heritability increases with age due to a decrease in unique environmental factors. Conclusion: The current findings illustrate the importance of genetic and environmental influences on four cytokines involved in the human immune response. For two of these there is evidence that heritability changes with age owing to changes in environmental factors unique to the individual.