Jasek Monika, Bojarska-Junak Agnieszka, Sobczyński Maciej, Wagner Marta, Chocholska Sylwia, Roliński Jacek, Wołowiec Dariusz, Karabon Lidia
Laboratory of Genetics and Epigenetics of Human Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.
Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland.
Cancers (Basel). 2020 Oct 6;12(10):2873. doi: 10.3390/cancers12102873.
Interactions between APRIL (TNFSF13) and its receptor TACI (TNFRSF13B) are implicated in providing survival benefits for chronic lymphocytic leukaemia (CLL) cells. Here we explored the relationship between and SNPs and expression of APRIL and TACI molecules and performed extended case-control study to evaluate earlier observations. Expression of APRIL and TACI was detected by FACS for 72 and 145 patients, respectively, and soluble APRIL was measured by ELISA in plasma of 122 patients. Genotypes were determined in 439 CLL patients and 477 control subjects with TaqMan Assays or restriction fragment length polymorphism (RFLP). The rs4968210GG genotype of was associated with a lower percentage of CD19APRIL cells in CLL patients when compared to (AA + GA) genotypes (-value = 0.027). Homozygosity at rs11078355 was associated with higher CD19 TACI cell percentage in CLL patients (-value = 0.036). The analysis of extended groups of patients and healthy controls confirmed the association of rs3803800AA genotype with a higher CLL risk (OR = 2.13; CI95% = 1.21; 3.75; -value = 0.007), while the possession of rs4985726G allele (CG + GG) genotype was associated with lower risk of CLL (OR = 0.69; CI95% = 0.51; 0.95; -value = 0.02). Genetic variants of and may have an impact on APRIL and TACI expression and may be considered as possible CLL risk factors.
增殖诱导配体(APRIL,TNFSF13)与其受体跨膜激活剂和钙调亲环素配体相互作用分子(TACI,TNFRSF13B)之间的相互作用被认为可为慢性淋巴细胞白血病(CLL)细胞提供生存益处。在此,我们探究了APRIL和TACI基因单核苷酸多态性(SNPs)与APRIL和TACI分子表达之间的关系,并进行了扩展病例对照研究以评估早期观察结果。分别通过荧光激活细胞分选术(FACS)检测了72例和145例患者的APRIL和TACI表达,通过酶联免疫吸附测定(ELISA)检测了122例患者血浆中的可溶性APRIL。采用TaqMan检测法或限制性片段长度多态性(RFLP)对439例CLL患者和477例对照者进行基因分型。与(AA + GA)基因型相比,APRIL基因的rs4968210GG基因型与CLL患者中CD19⁺APRIL⁺细胞的百分比降低相关(P值 = 0.027)。rs11078355位点的纯合性与CLL患者中较高的CD19⁺TACI⁺细胞百分比相关(P值 = 0.036)。对更多患者和健康对照人群的分析证实,APRIL基因的rs3803800AA基因型与较高的CLL风险相关(比值比[OR] = 2.13;95%置信区间[CI95%] = 1.21;3.75;P值 = 0.007),而TACI基因的rs4985726G等位基因(CG + GG)基因型与较低的CLL风险相关(OR = 0.69;CI95% = 0.51;0.95;P值 = 0.02)。APRIL和TACI的基因变异可能会影响APRIL和TACI的表达,并可能被视为CLL的潜在风险因素。