Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

• Published in: Genes and immunity Vol. 3; no. 7; pp. 407 - 413
• Main Authors: Reuss, E, Fimmers, R, Kruger, A, Becker, C, Rittner, C, Höhler, T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2002; Nature Publishing Group
• Subjects: Affinity; Alleles; Binding Sites - genetics; Biomedical and Life Sciences; Biomedicine; Body mass index; Cancer Research; Cell Line; Cytokines; DNA - metabolism; Electrophoretic mobility; Electrophoretic Mobility Shift Assay; Environmental factors; Female; full-paper; Gene Expression; Gene Expression Regulation - physiology; Genes, Reporter; Genetic aspects; Genetic factors; Genetic regulation; Haplotypes; Heritability; Human Genetics; Humans; Immune response; Immunology; In Vitro Techniques; Interleukin 10; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Lipopolysaccharides; Male; Monocytes; Monocytes - physiology; Physiological aspects; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; PU.1 protein; Reporter gene; Single-nucleotide polymorphism; Smoking; Transcription factors; Transcription Factors - metabolism; Twin studies; Twin Studies as Topic; Twins; Germany; twins; monocytes; single nucleotide polymorphisms; interleukin-10; smoking; heritability
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6363920

Interleukin-10 (IL-10) has a critical role in the regulation of immune responses. The relative contribution of genetic and environmental factors to IL-10 production is under debate. We performed a twin study in 246 monozygotic and dizygotic twins to assess the heritability of IL-10 production after LPS stimulation in whole blood. In addition, the influence of promoter single nucleotide polymorphisms (−1082, −819 and −592) on transcriptional activity and their binding to nuclear factors was studied in luciferase reporter gene and electrophoretic mobility shift assays. IL-10 production showed a genetic determination with a heritability of 0.5. Decreasing body mass index (BMI), smoking and female gender lead to decreased IL-10 production. In monocytes, the −1082A allele showed higher binding affinity to the transcription factor PU.1 resulting in decreased transcriptional activity of −1082A promoter haplotypes. Genetic determination of IL-10 secretion is probably lower than that previously reported. Fifty percent of the observed variability explained by genetic factors. Female individuals produce less IL-10 than male subjects. Environmental factors like smoking and decreasing BMI exert suppressing effects on IL-10 production. Although the −1082A allele shows higher binding affinity to the PU.1 transcription factor and lower transcriptional activity, this polymorphism probably explains only a small fraction of the observed heritability.