扩张型心肌病患者外周血中NAPSA基因rs10952362位点多态性与左心室逆重构的关系研究OA

Objective To detect the Napsin A aspartic peptidase(NAPSA)gene expression in peripheral blood of patients with dilated cardiomyopathy(DCM),and to further analyze the relationship between the NAPSA gene expression level and the single nucleotide polymorphism(SNPs)of rs10952362 locus and the genetic susceptibility of DCM and left ventricular reverse remodeling(LVRR).Methods A total of 134 DCM patients admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2023 to May 2024 were retrospectively enrolled.All patients received standard anti-heart failure drug therapy.The patients were divided into LVRR group(n=41)and non-LVRR group(n=93)according to whether LVRR reached the standard at the last review after treatment,and 100 healthy subjects were enrolled as controls.The SNPs of NAPSA gene rs10952362 were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The genetic equilibrium of NAPSA gene was tested by Hardy-Weinberg equilibrium test.Logistic regression model was used to analyze the association of rs10952362 polymorphism with the genetic susceptibility of DCM and LVRR.The mRNA expression level of NAPSA gene was detected by quantitative real-time PCR(RT-qPCR).Receiver operating characteristic(ROC)curve was used to analyze the predictive value of NAPSA gene expression for DCM and LVRR.Results The distribution of NAPSA gene rs10952362 genotype in the control group and the DCM group was in accordance with the Hardy-Weinberg genetic equilibrium law(χ2=0.379,1.963,all P>0.05),representative of the group.The frequencies of TT genotype(20.00%vs 37.31%)and T allele(43.00%vs 57.84%)at rs10952362 locus in DCM group were significantly higher than those in control group,and the differences were statistically significant(χ2=9.312,10.092,all P<0.05).Compared with the non-LVRR group,the frequency of TT genotype(24.39%vs 43.01%)and T allele(45.12%vs 63.44%)at rs10952362 in the LVRR group was significantly lower,and the differences were statistically significant(χ2=6.915,7.832,all P<0.05).Logistic regression analysis showed that the risk of DCM in the TT genotype group was 1.703 times higher than that in the CC genotype group(P=0.026).Compared with the TT genotype,the CC genotype was 1.509 times more likely to develop LVRR after standard anti-heart failure drug treatment(P=0.033).Compared with the control group,the relative expression levels of NAPSA mRNA in LVRR group and non-LVRR group were significantly increased(1.32±0.26,1.57±0.31 vs 0.99±0.17),and the NAPSA mRNA in non-LVRR group was higher than that in LVRR group,and the differences were statistically significant(t=26.633,40.389,4.691,all P<0.05).When the cut-off value of NAPSA mRNA was 1.23 and 1.46,the area under the curve(AUC)of NAPSA mRNA in predicting DCM and LVRR were 0.883 and 0.857,respectively,and the sensitivity were 88.3%and 83.7%,the specificity were 82.5%and 78.5%,respectively.Conclusions The NAPSA gene rs10952362 polymorphism is closely related to the genetic susceptibility of DCM and ventricular reverse remodeling.Patients with TT genotype have a higher risk of DCM and a lower incidence of LVRR after treatment.NAPSA mRNA expression in peripheral blood of DCM patients is significantly increased,which can be used as a predictor for early diagnosis and evaluation of LVRR in DCM patients.