CHIP相关基因与MPN患者心脑血管事件的风险分析  

Analysis of CHIP-Related Mutation and Risk of Cardio-Cerebrovasculars Events in Patients with Myeloproliferative Neoplasms

作　　者：韩雪[1] 白贝贝[1] 冯翠翠 赵森[1] 陈烨[1] HAN Xue;BAI Bei-Bei;FENG Cui-Cui;ZHAO Sen;CHEN Ye(Department of Hematology,Beiing Anzhen Hospital,Capital Medical University,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院血液科,北京100029

出　　处：《中国实验血液学杂志》2024年第1期190-196,共7页Journal of Experimental Hematology

摘　　要：目的:分析骨髓增殖性肿瘤(MPN)患者不确定潜能的克隆性造血(CHIP)相关基因突变谱和临床特征,探讨CHIP相关基因与其心脑血管事件(CCE)的相关性及可能作用机制。方法:回顾性分析2019年8月-2022年7月首都医科大学附属北京安贞医院血液科收治的73例MPN患者的临床资料和二代测序结果,采用Logistic回归分析CHIP相关基因、炎症细胞因子对MPN患者CCE的影响。结果:55例(75.3%)MPN患者检出CHIP相关基因,原发性血小板增多症(ET)和真性红细胞增多症(PV)患者CHIP相关基因各突变频率差异无统计学意义。CHIP相关基因突变以单基因形式为主,检出率从高至低依次为JAK2V617F(63.0%,46/73)、ASXL1(16.4%,12/73)、TET2(11.0%,8/73)、DNMT3A(9.6%,7/73)、SRSF2(6.9%,5/73)、SF3B1(4.1%,3/73)、TP53(1.4%,1/73)和PPMID(1.4%,1/73)。年龄>60岁患者CHIP相关基因检出率明显高于≤60岁者[91.7%(33/36)vs 59.5%(22/37)]。27例(37.0%)MPN患者伴CCE(MPN/CCE),2次CCE者5例,均为动脉事件。CCE组患者年龄(62.8±12.8 vs 53.9±15.8岁,P=0.015)、IL-1β水平(17.7±26.0vs 4.3±8.6,P=0.012)、IL-8水平(360.7±598.6 vs 108.3±317.0,P=0.045)、血栓形成史(29.6%vs 2.2%,P=0.020)和CHIP相关基因检出率(88.9%vs 67.4%,P=0.040)高于无CCE组。多因素Logistic回归分析结果显示,年龄(OR=0.917,95%CI:0.843-0.999,P=0.047)、血栓形成史(OR=34.148,95%CI:2.392-487.535,P=0.009)、任何1个CHIP相关基因突变(OR=16.065,95%CI:1.217-212.024,P=0.035)和IL-1β水平升高(OR=0.929,95%CI:0.870-0.992,P=0.027)均是MPN/CCE的独立危险因素;CHIP相关单基因突变与MPN/CCE无关,但DNMT3A(OR=88.717,95%CI:2.690-292.482,P=0.012)、ASXL1(OR=7.941,95%CI:1.045-60.353,P=0.045)突变是PV/CCE的独立危险因素。结论:MPN患者CHIP相关基因突变率高,尤其是60岁以上患者;高龄、血栓形成史、CHIP相关基因突变和IL-1β水平升高是MPN发生CCE的独立危险因素。DNMT3A、ASXL1单基因突变是PV患者CCE的独立危险因素。CHIP相关基因突Objective:To analyze the mutant spectrum of clonal hematopoiesis of indeterminate potential(CHIP)related mutations and clinical characteristics and to explore the correlation and the possible mechanism between CHIP-related mutations and cardio-cerebrovasculars events(CCEs)in patients with myeloproliferative neoplasms(MPNs).Methods:The clinical data and next-generation sequencing results of 73 MPN patients in Beijing Anzhen Hospital from August 2019 to July 2022 were retrospectively analyzed.Statistical analyses were conducted by multivariate logistic regression for the effects of CHIP-related mutations and inflammatory cytokines on CCEs for MPNs patients.Results:Fifty-five cases of MPN(75.3%)showed positive in CHIP-related genes.There was no significant difference in variant allele frequency of CHIP-related gene between essential thrombocythemia(ET)and polycythemia vera(PV).CHIP-related gene mutations were mainly single gene mutations,with mutation rate from high to low as JAK2V617F(63.0%,46/73),ASXL1(16.4%,12/73),TET2(11.0%,8/73),DNMT3A(9.6%,7/73),SRSF2(6.9%,5/73),SF3B1(4.1%,3/73),TP53(1.4%,1/73)and PPM1D(1.4%,1/73).The mutation rate of CHIP-related genes in MPN patients>60 years old was significantly higher than that in the patients≤60 years old[91.7%(33/36)vs 59.5%(22/37)].CCEs occurred in 27 MPNs patients(37.0%,MPNs/CCEs),and 5 had recurrent CCEs,all of which were arterial events.Age(62.8±12.8 years vs 53.9±15.8 years,P=0.015),IL-1βlevel(17.7±26.0 vs4.3±8.6,P=0.012),IL-8 level(360.7±598.6 vs 108.3±317.0,P=0.045),the proportion of the patients w ith thrombosis history(29.6%vs 2.2%,P=0.020),and the detection rate of CHIP-related mutations(88.9%vs67.4%,P=0.040)in the group with CCEs were higher than those in the group w ithout CCEs.M ultivariate Logistic regression analysis showed that age(OR=0.917,95%CI:0.843-0.999,P=0.047),thrombosis history(OR=34.148,95%CI:2.392-487.535,P=0.009),any CHIP-related mutations(OR=16.065,95%CI:1.217-212.024,P=0.035),and elevated level of IL-1β(OR=0.929,95%CI:0.870-0.992,P

关 键 词：骨髓增殖性肿瘤 CHIP相关基因 心脑血管事件 炎症细胞因子 

分 类 号：R733.3[医药卫生—肿瘤]