<i>ICOS</i> gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

Abstract

Abstract:There is strong evidence that altered immunological function entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). The main mechanism of an anti-tumor response depends on T-cell activation. Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, the upregulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal antibody responses to T cell-dependent antigens. It does not upregulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Our previous results indicated the ICOS gene has a role as a susceptibility locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in the Polish population. A case-control study of 296 individuals, including 146 B-CLL patients, was conducted on four polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOS ISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was carried out using allelic discrimination methods with the TaqMan ® SNP Genotyping Assay. There were no statistically significant differences in the allele, genotype, or haplotype distributions between B-CLL patients and healthy controls for any of the investigated polymorphic markers in the ICOS gene.

Association of Inducible T Cell Costimulator Polymorphisms with Susceptibility and Outcome of Hepatitis B Virus Infection in a Chinese Han Population

“…In our current study, it was found that the allele 'A' of rs1559931 had a protective effect on HCC development in CHB and HBV-associated LC patients. In addition, rs4675379 has been proposed to be associated with the progression of B cell chronic lymphocytic leukaemia, but no relation was found in type 1 diabetes susceptibility or the outcome of kidney transplantation [20,33,38]. Our current data showed that distribution of the rs4675379 CC genotype was different between HBV infection and clearance, but there was no statistical difference found among the GC genotype, GG&GC+CC and C allele.…”

“…Moreover, 5'-untranslated region may also function to regulate gene splicing [30,31]. Being a neighbour to CTLA-4, rs10932029 polymorphism has been reported to affect expression of the CTLA-4 isoforms and be associated with sporadic breast cancer and the disease dynamics of B cell chronic lymphocytic leukaemia [19,20]. However, studies on kidney transplantation and malignant melanoma did not show any significant association with rs10932029 polymorphism [32,33].…”

“…Three tagging SNPs (rs11883722, rs4675379 and rs1559931) were then selected from these blocks based on functional prediction of these variants using the online Web server F-SNP (http://compbio.cs.queensu.ca/F-SNP/). rs10932029 was also selected because it is associated with breast cancer and B cell chronic lymphocytic leukaemia [19,20].…”

Association of polymorphisms in the <i>ICOS</i> and <i>ICOSL</i> genes with the pathogenesis of autoimmune thyroid diseases

“…The second SNP is rs10932029 T/C (termed ICOS SNP2) located in the intron region. It has been reported that patients with B-cell chronic lymphocytic leukemia who have the C allele show disease worsening [28]. In ICOS SNP2, comparing the T allele and C allele, those who have the C allele demonstrated a significantly increased risk of breast cancer [30].…”

“…The first SNP in ICOS is rs10183087 A/C (termed ICOS SNP1) located in the 3'-UTR, and it is reported that patients with B-cell chronic lymphocytic leukemia who have the AA genotype of this SNP were protected against heavy progression of this disease [28]. Patients with the AA+AC genotype showed a delayed graft function outcome of kidney transplantation [29].…”