Association of Common Variants of TNFSF13 and TNFRSF13B Genes with CLL Risk and Clinical Picture, as Well as Expression of Their Products-APRIL and TACI Molecules.
Association of Common Variants of TNFSF13 and TNFRSF13B Genes with CLL Risk and Clinical Picture, as Well as Expression of Their Products-APRIL and TACI Molecules.
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DOI：
10.3390/cancers12102873
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发表时间：
2020-10-06
期刊：
影响因子：
5.2
通讯作者：
Karabon L
中科院分区：
文献类型：
--
作者：
Jasek M;Bojarska-Junak A;Sobczyński M;Wagner M;Chocholska S;Roliński J;Wołowiec D;Karabon L
越来越多的文献报道表明，APRIL在慢性淋巴细胞白血病(CLL)的发生发展中起着重要作用，尤其是CLL细胞中sAPRIL水平的升高及其mRNA的过度表达。此外，在体外，TACI的表达被发现可以提高CLL细胞的存活能力，保护它们免受凋亡的影响。另一方面，有证据支持存在患慢性淋巴细胞性白血病的遗传倾向。这些数据促使我们研究TNFSF13和TNFRSF13B的遗传变异对这些基因编码的蛋白质表达水平的影响，并调查这些变异与CLL风险的关系。APRIL(TNFSF13)和其受体TACI(TNFRSF13B)之间的相互作用可能有助于慢性淋巴细胞白血病(CLL)细胞的生存。在这里，我们探讨了TNFSF13和TNFRSF13B SNPs与APRIL和TACI分子表达的关系，并进行了扩大的病例对照研究以评估早期的观察结果。用流式细胞仪分别检测72例和145例患者血浆中APRIL和TACI的表达，用ELISA法检测122例患者血浆中可溶性APRIL的水平。采用TaqMan法或限制性片段长度多态(RFLP)方法对439例CLL患者和477例正常对照进行了基因分型。在慢性淋巴细胞性白血病患者中，rs4968210GG型与(AA+GA)型相比，CD19+APRIL+细胞百分率降低(p值=0.027)。在慢性淋巴细胞性白血病患者中，rs11078355TNFRSF13B纯合子与较高的CD19+TACI+细胞百分比相关(p值=0.036)。对患者和健康对照组的分析证实，TNFSF13rs3803800AA基因型与慢性淋巴细胞性白血病的风险相关(OR=2.13；CI95%=1.21；3.75；p值=0.007)，而拥有TNFFSF13Brs4985726G等位基因(CG+GG)与慢性淋巴细胞性白血病的风险相关(OR=0.69；CI95%=0.510.95；p值=0.02)。TNFSF13和TNFRSF13B基因变异可能对APRIL和TACI的表达产生影响，可能被认为是CLL的可能危险因素。
A growing body of evidence reported in literature suggests an important role of APRIL in the development and pathogenesis of chronic lymphocytic leukaemia (CLL), in particular elevated levels of soluble APRIL (sAPRIL) and overexpression of its mRNA have been noticed in CLL cells. Moreover, TACI expression has been found to improve the survival ability of CLL cells protecting them from apoptosis in vitro. On the other hand, there are evidence supporting the existence of a genetic predisposition to develop CLL. These data prompted us to investigate the influence of genetic variants of TNFSF13 and TNFRSF13B on the expression level of proteins encoded by these genes and to investigate the association between these variants an CLL risk. 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 TNFSF13 and TNFRSF13B 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 TNFSF13 was associated with a lower percentage of CD19+APRIL+ cells in CLL patients when compared to (AA + GA) genotypes (p-value = 0.027). Homozygosity at rs11078355 TNFRSF13B was associated with higher CD19+ TACI+ cell percentage in CLL patients (p-value = 0.036). The analysis of extended groups of patients and healthy controls confirmed the association of TNFSF13 rs3803800AA genotype with a higher CLL risk (OR = 2.13; CI95% = 1.21; 3.75; p-value = 0.007), while the possession of TNFRSF13B rs4985726G allele (CG + GG) genotype was associated with lower risk of CLL (OR = 0.69; CI95% = 0.51; 0.95; p-value = 0.02). Genetic variants of TNFSF13 and TNFRSF13B may have an impact on APRIL and TACI expression and may be considered as possible CLL risk factors.
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DOI：
10.1038/nrdp.2016.96
发表时间：
2017-01-19
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Kipps TJ;Stevenson FK;Wu CJ;Croce CM;Packham G;Wierda WG;O'Brien S;Gribben J;Rai K
通讯作者：
Rai K
影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
13
作者：
Mackay, Fabienne;Schneider, Pascal
通讯作者：
Schneider, Pascal
影响因子：
12.8
作者：
Hallek, Michael
通讯作者：
Hallek, Michael
影响因子：
30.8
作者：
Lonsdale, John;Thomas, Jeffrey;Salvatore, Mike;Phillips, Rebecca;Lo, Edmund;Shad, Saboor;Hasz, Richard;Walters, Gary;Garcia, Fernando;Young, Nancy;Foster, Barbara;Moser, Mike;Karasik, Ellen;Gillard, Bryan;Ramsey, Kimberley;Sullivan, Susan;Bridge, Jason;Magazine, Harold;Syron, John;Fleming, Johnelle;Siminoff, Laura;Traino, Heather;Mosavel, Maghboeba;Barker, Laura;Jewell, Scott;Rohrer, Dan;Maxim, Dan;Filkins, Dana;Harbach, Philip;Cortadillo, Eddie;Berghuis, Bree;Turner, Lisa;Hudson, Eric;Feenstra, Kristin;Sobin, Leslie;Robb, James;Branton, Phillip;Korzeniewski, Greg;Shive, Charles;Tabor, David;Qi, Liqun;Groch, Kevin;Nampally, Sreenath;Buia, Steve;Zimmerman, Angela;Smith, Anna;Burges, Robin;Robinson, Karna;Valentino, Kim;Bradbury, Deborah;Cosentino, Mark;Diaz-Mayoral, Norma;Kennedy, Mary;Engel, Theresa;Williams, Penelope;Erickson, Kenyon;Ardlie, Kristin;Winckler, Wendy;Getz, Gad;DeLuca, David;MacArthur, Daniel;Kellis, Manolis;Thomson, Alexander;Young, Taylor;Gelfand, Ellen;Donovan, Molly;Meng, Yan;Grant, George;Mash, Deborah;Marcus, Yvonne;Basile, Margaret;Liu, Jun;Zhu, Jun;Tu, Zhidong;Cox, Nancy J.;Nicolae, Dan L.;Gamazon, Eric R.;Im, Hae Kyung;Konkashbaev, Anuar;Pritchard, Jonathan;Stevens, Matthew;Flutre, Timothee;Wen, Xiaoquan;Dermitzakis, Emmanouil T.;Lappalainen, Tuuli;Guigo, Roderic;Monlong, Jean;Sammeth, Michael;Koller, Daphne;Battle, Alexis;Mostafavi, Sara;McCarthy, Mark;Rivas, Manual;Maller, Julian;Rusyn, Ivan;Nobel, Andrew;Wright, Fred;Shabalin, Andrey;Feolo, Mike;Sharopova, Nataliya;Sturcke, Anne;Paschal, Justin;Anderson, James M.;Wilder, Elizabeth L.;Derr, Leslie K.;Green, Eric D.;Struewing, Jeffery P.;Temple, Gary;Volpi, Simona;Boyer, Joy T.;Thomson, Elizabeth J.;Guyer, Mark S.;Cathy Ng;Abdallah, Assya;Colantuoni, Deborah;Insel, Thomas R.;Koester, Susan E.;Little, A. Roger;Bender, Patrick K.;Lehner, Thomas;Yao, Yin;Compton, Carolyn C.;Vaught, Jimmie B.;Sawyer, Sherilyn;Lockhart, Nicole C.;Demchok, Joanne;Moore, Helen F.
通讯作者：
Moore, Helen F.