56例肺动脉高压患者遗传学特征及血流动力学表现分析

Analysis of genetic characteristics and hemodynamics in 56 patients with pulmonary hypertension

目的:分析56例肺动脉高压(PAH)患者遗传学特征及血流动力学表现,评估两者间的相关性。方法:收集2014年4月—2021年5月在武汉亚洲心脏病医院明确诊断肺动脉高压并接受基因检测排查遗传学病因的56例患者,按基因检测结果分为阳性组(突变提示致病或可能致病)和提示关注组(突变提示临床意义不明),比较不同基因检测结果患者实验室检查结果及血流动力学指标差异,分析基因突变与PAH患者临床表现之间的关系。结果:56例患者中基因检测阳性组患者25例,提示关注组患者31例,两组患者性别、年龄、BMI等一般资料相比差异无统计学意义;阳性组检测出突变基因8个,携带率最高的是BMPR2基因,提示关注组检测出可能致病的突变基因26个,携带率最高的是RNF213基因。阳性组与提示关注组患者心功能分级差异无统计学意义;血流动力学比较结果显示,阳性组肺循环阻力(PVR)高于提示关注组(χ2=6.570,P=0.037);阳性组中BMPR2突变与其他基因突变相比血流动力学差异无统计学意义;超声心动图指标差异无统计学意义;生化指标结果显示,阳性组谷丙转氨酶(ALT)高于提示关注组(t=2.023,P=0.047)。结论:56例PAH患者致病突变发生率44.64%;可能致病突变发生率55.36%,携带突变基因的患者表现出更高的肺血管阻力,提示这些患者肺血管病变更重,可能需要更强化的治疗。

Objective To analyze the genetic and hemodynamic characteristics of 56 patients with pulmonary hypertension(PAH) and evaluate the correlation between them.Methods The 56 patients with PAH who were definitely diagnosed in Wuhan Asian Heart Hospital from April 2014 to May 2021 and who underwent gene testing for genetic causes were collected. According to the results of gene testing, they were divided into positive group(mutation indicates pathogenicity or possible pathogenicity) and prompt concern group(mutation indicates unclear clinical significance). The differences of laboratory test results and hemodynamic indicators among patients with different gene testing results were compared. We analyzed the relationship between gene mutation and clinical manifestations of PAH patients.Results Among the 56 patients, 25 patients were in the gene detection positive group, indicating that 31 patients in the concern group had no significant difference in general information such as gender, age, BMI between the two groups(P>0.05);Eight mutated genes were detected in the positive group, and BMPR2 gene had the highest carrying rate, indicating that 26 mutated genes that might cause disease were detected in the concerned group, and RNF213 gene had the highest carrying rate. There was no significant difference between the positive group and the prompt concern group in heart function grading(P>0.05). The results of hemodynamic comparison showed that the PVR of positive group was higher than that of prompt concern group(χ2=6.570, P=0.037). There was no significant difference in hemodynamics between BMPR2 mutation and other gene mutations in the positive group(P>0.05). There was no significant difference in the results of echocardiography(P>0.05). The results of biochemical indicators showed that ALT in the positive group was higher than that in the prompt concern group(t=2.023, P=0.047).Conclusion The incidence of pathogenic mutations in 56 PAH patients was 44.64%. The incidence of possible pathogenic mutations was 55.36%, and patients carrying the mutation gene showed higher pulmonary vascular resistance, indicating that these patients had more severe pulmonary vascular disease and might need more intensive treatment.