Variations in Suppressor Molecule CTLA-4 Gene Are Related to Susceptibility to Multiple Myeloma in a Polish Population

• Published in: Pathology oncology research Vol. 18; no. 2; pp. 219 - 226
• Main Authors: Karabon, Lidia, Pawlak-Adamska, Edyta, Tomkiewicz, Anna, Jedynak, Anna, Kielbinski, Marek, Woszczyk, Dariusz, Potoczek, Stanisław, Jonkisz, Anna, Kuliczkowski, Kazimierz, Frydecka, Irena
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.04.2012; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; CTLA-4 Antigen - genetics; DNA - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes - genetics; Humans; Immunology; Male; Middle Aged; Multiple Myeloma - epidemiology; Multiple Myeloma - genetics; Oncology; Pathology; Phenotype; Poland - epidemiology; Polymerase Chain Reaction; Polymorphism, Genetic - genetics; Prognosis; Poland; MM; Gene polymorphisms; CTLA-4
• ISSN: 1219-4956; 1532-2807
• DOI: 10.1007/s12253-011-9431-6

Various phenotype and functional T-cell abnormalities are observed in multiple myeloma (MM) patients. The aim of this study was to investigate the association between polymorphisms in the gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of the T-lymphocyte immune response and susceptibility to multiple myeloma in a Polish population. Two hundred MM patients and 380 healthy subjects were genotyped for the following polymorphisms: CTLA-4 c.49A>G, CTLA-4 g.319C>T, CTLA-4 g.*642AT(8_33), CT60 ( CTLA-4 g.*6230G>A), Jo31 ( CTLA-4 g.*10223G>T). Our study is the largest and most comprehensive evaluation to date of the association between genetic polymorphisms in the CTLA-4 molecule and multiple myeloma. It was found that CTLA-4 c.49A>G[G], CT60[G], and Jo31[G] alleles were more frequently observed in MM patients than in controls (0.50 vs. 0.44, p  = 0.03, 0.65 vs. 0.58, p  = 0.04, and 0.63 vs. 0.57, p  = 0.03, respectively). Moreover, the haplotype CTLA-4 c.49A>G[G], CTLA-4 g.319C>T[C], CTLA-4 g.*642AT(8_33) [ 8 ], CT60[G], Jo31[G] including all susceptibility alleles increases the risk of MM about fourfold (OR: 3.79, 95%CI: 2.08–6.89, p  = 0.00001). These findings indicate that genetic variations in the CTLA-4 gene play role in susceptibility to multiple myeloma and warrant further investigation through replication studies.