Polymorphisms in the TNF-α Promoter and Variability in the Granulomatous Response in Patients with Crohn's Disease

Dalal, Ilan; Karban, Amir; Wine, Eytan; Eliakim, Rami; Shirin, Haim; Fridlender, Marcelo; Shaoul, Ron; Leshinsky‐Silver, Esther; Levine, Arie

doi:10.1203/01.pdr.0000215028.19269.94

Cited by 4 publications

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“…Each of the polymorphisms was genotyped in our COMD study sample, and the resulting allele frequencies, as determined from the parental chromosomes, are shown in table 2 . All of the frequencies are similar to those that have been reported previously for these polymorphisms elsewhere [81,90,93,94,99,[105][106][107][108][109] .…”

Section: Resultssupporting

confidence: 88%

Cytokine Genes TNF, IL1A, IL1B, IL6, IL1RN and IL10, and Childhood-Onset Mood Disorders

et al. 2008

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Background/Aims: Inflammatory cytokines induce a behavioral syndrome, known as sickness behavior, that strongly resembles symptoms typically seen in depression. This resemblance has led to the theory that an imbalance of inflammatory cytokine activity may be a contributing factor in depressive disorders. Support for this is found in multiple lines of evidence, such as the effects of cytokines on the activities of the hypothalamic-pituitary-adrenal axis, serotonin and brain-derived neurotrophic factor, and hippocampal function, all of which are implicated in the etiology of depression. In addition, associations between inflammatory activity and depressive symptomology have been documented in a number of studies, and the depressogenic effects of cytokine therapy are well known. Accordingly, given that depression has a substantial genetic basis, genes involved in the regulation of inflammatory cytokine activity are strong candidates for involvement in genetic susceptibility to depressive disorders. Here, we have tested 6 key genes of this type, TNF, IL1A, IL1B, IL6, IL1RN and IL10, as candidates for involvement in childhood-onset mood disorders. Methods: In this study of 384 families, each ascertained through a child with depression diagnosed before the age of 15 years, 11 polymorphisms of known or likely functional significance (coding and regulatory variants) were analyzed. Results: Testing for biased transmission of alleles from parents to their affected offspring, we found no evidence for an association between childhood-onset mood disorders and any of the polymorphisms, either individually or as haplotypes. Conclusion: The present study does not support the involvement of the TNF, IL1A, IL1B, IL6, IL1RN and IL10 variants as major genetic risk factors contributing to early-onset mood disorders.

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