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
Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Department and Clinic of Urology, Wroclaw Medical University, Wroclaw, Poland.
Arch Immunol Ther Exp (Warsz). 2016 Dec;64(Suppl 1):137-145. doi: 10.1007/s00005-016-0430-x. Epub 2016 Dec 8.
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.
本研究的目的是确定编码B和T淋巴细胞衰减器（BTLA）的基因多态性与慢性淋巴细胞白血病（CLL）易感性之间的关联，以及它们对CLL患者（pts.）T和B细胞中BTLA基因mRNA表达的影响。使用TaqMan探针，对321例CLL患者和470例对照进行了以下BTLA单核苷酸多态性（SNP）的基因分型：rs2705511、rs1982809、rs9288952、rs76844316、rs16859633、rs9288953、rs2705535、rs1844089、rs2705565、rs2633580。使用Applied Biosystems检测法测定了37例CLL患者T和B细胞亚群中人BTLA的mRNA水平。三个SNP：rs1982809、rs2705511和rs9288953与CLL易感性相关。与对照组相比，患者中rs1982809[G]等位基因和rs2705511[C]等位基因携带者的频率更高（分别为0.51对0.41，OR 1.51，95%CI 1.14 - 2.02，p = 0.004；以及0.56对0.44，OR 1.62，95%CI 1.22 - 2.16，p = 0.0009）。此外，与对照组相比，rs9288953[TT]基因型在CLL患者中过度表达（0.22对0.14，OR 1.74，95%CI 1.20 - 2.53，p = 0.004）。对BTLA SNP对CLL患者中BTLA mRNA表达影响的评估表明，与[AA]纯合子相比，CLL患者T细胞中rs1982809[G]等位基因的存在与较低的中位数（±SD）BTLA mRNA表达相关（以2 - delta Ct表示）（0.009 ± 0.013对0.026 ± 0.012，p = 0.03）。我们的结果表明，rs1982809 BTLA基因多态性与mRNA表达水平相关，并且BTLA基因的变异可能被视为潜在的低穿透性CLL风险因素。
