Intragenic Variations in BTLA Gene Influence mRNA Expression of BTLA Gene in Chronic Lymphocytic Leukemia Patients and Confer Susceptibility to Chronic Lymphocytic Leukemia

• Published in: Archivum Immunologiae et Therapiae Experimentalis Vol. 64; no. Suppl 1; pp. 137 - 145
• Main Authors: Karabon, Lidia, Partyka, Anna, Jasek, Monika, Lech-Maranda, Ewa, Grzybowska-Izydorczyk, Olga, Bojarska-Junak, Agnieszka, Pawlak-Adamska, Edyta, Tomkiewicz, Anna, Robak, Tadeusz, Rolinski, Jacek, Frydecka, Irena
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2016; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Cohort Studies; Female; Gene Expression Regulation, Leukemic; Genetic Predisposition to Disease; Genotype; Humans; Immunology; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Male; Middle Aged; Original; Original Article; Pharmacology/Toxicology; Polymorphism, Single Nucleotide; Receptors, Immunologic - genetics; RNA, Messenger - metabolism; Treatment Outcome; BTLA; Gene polymorphisms; Chronic lymphocytic leukemia; mRNA expression
• ISSN: 0004-069X; 1661-4917
• DOI: 10.1007/s00005-016-0430-x

The aim of this study was to determine the association between polymorphisms in gene encoding B- and T-lymphocyte attenuator ( BTLA ) and susceptibility to chronic lymphocytic leukemia (CLL) and their influence on mRNA expression of BTLA gene in T and B cells from CLL patients (pts.). The following BTLA single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs76844316, rs16859633, rs9288953, rs2705535, rs1844089, rs2705565, rs2633580 were genotyped with use of TaqMan probes in 321 CLL pts. and in 470 controls. The mRNA levels of human BTLA were determined in subpopulations of T and B cells from 37 CLL patients with use of Applied Biosystems assays. Three SNPs: rs1982809, rs2705511 and rs9288953 were associated with susceptibility to CLL. The frequency of rs1982809[G] allele and rs2705511[C] allele carriers was higher in patients compared to the controls (0.51 vs. 0.41, OR 1.51, 95% CI 1.14–2.02, p  = 0.004 and 0.56 vs. 0.44, OR 1.62, 95% CI 1.22–2.16, p  = 0.0009, respectively). Furthermore, rs9288953[TT] genotype was overrepresented in CLL pts. compared to the controls (0.22 vs. 0.14, OR 1.74, 95% CI 1.20–2.53, p  = 0.004). The evaluation of the influence of BTLA SNPs on BTLA mRNA expression in CLL pts. showed that the presence of rs1982809[G] allele was associated with lower median (±SD) BTLA mRNA expression in T cells (expressed as 2-delta Ct) in CLL pts. as compared to [AA] homozygotes (0.009 ± 0.013 vs. 0.026 ± 0.012, p  = 0.03). Our results indicate that rs1982809 BTLA gene polymorphism is associated with mRNA expression level and that variations in the BTLA gene might be considered as potentially low-penetrating CLL risk factor.