Cytokine gene polymorphism in human disease: on-line databases

Abstract

The pathologies of many infectious, autoimmune and malignant diseases are influenced by the profiles of cytokine production in pro-inflammatory (TH1) and anti-inflammatory (TH2) T cells. Interindividual differences in cytokine profiles appear to be due, at least in part, to allelic polymorphism within regulatory regions of cytokine gene. Many studies have examined the relationship between cytokine gene polymorphism, cytokine gene expression in vitro, and the susceptibility to and clinical severity of diseases. A review of the findings of these studies is presented. An on-line version featuring appropriate updates is accessible from the World Wide Web site, http://www.pam.bris.ac.uk/services/GAI/cytokine4.htm.

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

“…Barbosa et al 44 showed that BeWo line trophoblasts are susceptible to invasion and replication, especially if they are Table 1 Human immune response genes: hypothetical effect of some polymorphisms on congenital toxoplasmosis Table 1). 32,35,[45][46][47] It is important to emphasize that BeWo cells are not models for the syncytiotrophoblast, the main mother/conceptus interface. Thus, these results would be related to local invasion of the placenta, but not necessarily to passage across the mother/embryo barriers.…”

“…They affect susceptibility or resistance to several infectious diseases. 45,46,[61][62][63][64] In addition, chemokine receptor signaling processes are important for leukocyte recruitment and controlled trophoblast invasion and thus for implantation and placentation. 25,26 CCR2 and CCR5 are chemokine receptors that have been assigned a function in toxoplasmosis and, independently in pregnancy, they protect from uncontrolled T. gondii replication in adults and favor trophoblast survival or invasion (related to a Th1 response), partially explaining the first-trimester resistance against vertical transmission.…”

“…Among reported singlenucleotide polymorphisms of TGF-b gene, the Arg25 is also related with an increased expression. 35,45,46 Highexpression polymorphisms of either TGF-b or IL-10 would protect the implanting embryo against sterile abortion or IFN-g/ICAM-1-facilitated vertical transmission, but would be negative for parasite-induced pathogenesis control in the conceptus already infected by T. gondii. The classical Th2 interleukin, IL-4, has been shown to be nonprotective in T. gondii-acquired infection in both humans and animals.…”

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

“…14 The SNPs are closely linked and only three haplotypes are found in Caucassian population (GCC, ACC, ATA). IL-10 microsatellite alleles and SNPs have been correlated with high and low IL-10 production after in vitro stimulation 14,15 and have been associated with several diseases (reviewed by Bidwell et al 16 ). However, data concerning the influence of the promoter SNPs on IL-10 production are still contradictory.…”

Characterization of new polymorphisms in the 5′UTR of the human interleukin-1 receptor type 1 (IL1R1) gene: linkage to type 1 diabetes and correlation to IL-1RI plasma level

“…13 It is presently unknown whether interindividual differences in IL1R1 expression or promoter usage are related to genetic variation within regulatory regions of the gene, though such associations have been reported in several other cytokine genes. 14 The IL-1 gene cluster has been implicated in genetic susceptibility to T1DM in several studies, but the data are controversial. We have previously reported association of a PstI polymorphism in this region to T1DM, 15 although a subsequent family-based study could not confirm this.…”