ICOS gene polymorphisms in B-cell chronic lymphocytic leukemia in the Polish population

• Published in: Folia histochemica et cytobiologica Vol. 49; no. 1; pp. 49 - 54
• Main Authors: Karabon, Lidia, Jedynak, Anna, Tomkiewicz, Anna, Wolowiec, Dariusz, Kielbinski, Marek, Woszczyk, Dariusz, Kuliczkowski, Kazimierz, Frydecka, Irena
• Format: Journal Article
• Language: English
• Published: Poland Wydawnictwo Via Medica 01.01.2011; Via Medica
• Subjects: Aged; Alleles; Antibodies; Antigens; Antigens, Differentiation, T-Lymphocyte - genetics; B-CLL; Case-Control Studies; CD28 antigen; Cell activation; Cell surface; Chronic lymphocytic leukemia; Cytokines; Disease Progression; Female; Follow-Up Studies; Gene polymorphism; Genotype; Genotyping; Haplotypes; Humans; ICOS; Immunology; Inducible T-Cell Co-Stimulator Protein; Interleukin 10; Interleukin 2; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphokines; Male; Middle Aged; Neoplasm Staging; Poland; Polymorphism, Genetic - genetics; polymorphisms; Population studies; Single-nucleotide polymorphism; Statistical analysis; Susceptibility; Tumors; Poland
• ISSN: 0239-8508; 1897-5631
• DOI: 10.5603/fhc.2011.0008

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. However, we noted that patients carrying genotype ICOS ISV1+173T>C [TT], ICOSc.602A>C [AA], ICOSc.1624C>T [CC], and ICOSc.2373G>C [GG] have a decreased frequency of progression to a higher Rai stage during 60-month follow-up (21.35% vs. 40.8%, p = 0.013) compared to other individuals. This indicates that the investigated polymorphisms do not modulate the risk of B-CLL in the Polish population, but are associated with disease dynamics, in particular with the time to Rai stage progression.