title: Intragenic Variations in BTLA Gene Influence mRNA Expression of BTLA Gene in Chronic Lymphocytic Leukemia Patients and Confer Susceptibility to Chronic Lymphocytic Leukemia.
abstract: 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.
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. lkarabon@iitd.pan.wroc.pl.|Department and Clinic of Urology, Wroclaw Medical University, Wroclaw, Poland. lkarabon@iitd.pan.wroc.pl.
authors.forename: Lidia
authors.identifier: http://orcid.org/0000-0001-8172-0971
authors.initials: L
authors.lastname: Karabon
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Partyka
authors.affiliation: Department of Clinical Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Jasek
authors.affiliation: Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.|Department of Hematology and Transfusion Medicine, Centre of Postgraduate Medical Education, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Lech-Maranda
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Grzybowska-Izydorczyk
authors.affiliation: Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bojarska-Junak
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Pawlak-Adamska
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Tomkiewicz
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Lublin, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Rolinski
authors.affiliation: Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Frydecka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C482586:BTLA protein, human; D012333:RNA, Messenger; D011971:Receptors, Immunologic
keywords: BTLA; Chronic lymphocytic leukemia; Gene polymorphisms; mRNA expression