title: Variations in suppressor molecule ctla-4 gene are related to susceptibility to multiple myeloma in a polish population.
abstract: 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-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CT60 (CTLA-4g.*6230G>A), Jo31 (CTLA-4g.*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-4c.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-4c.49A>G[G], CTLA-4g.319C>T[C], CTLA-4g.*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.
authors: Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wroclaw, Poland. lkarabon@iitd.pan.wroc.pl
authors: Lidia
authors: L
authors: Karabon
authors: Edyta
authors: E
authors: Pawlak-Adamska
authors: Anna
authors: A
authors: Tomkiewicz
authors: Anna
authors: A
authors: Jedynak
authors: Marek
authors: M
authors: Kielbinski
authors: Dariusz
authors: D
authors: Woszczyk
authors: Stanisław
authors: S
authors: Potoczek
authors: Anna
authors: A
authors: Jonkisz
authors: Kazimierz
authors: K
authors: Kuliczkowski
authors: Irena
authors: I
authors: Frydecka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000453:epidemiology* / Q000235:genetics*; D010641:Phenotype; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis
chemical_list: D060908:CTLA-4 Antigen; D004247:DNA