THR mRNA、ALCAT1在甲亢性心脏病中的协同诊断作用

Synergistic diagnosis of THR mRNA and ALCAT1 in hyperthyroidism heart disease

目的探讨甲状腺激素受体(THR)mRNA、心磷脂酰基转移酶1(ALCAT1)在甲亢性心脏病中的临床意义。方法选取2020年2月—2022年3月张家口市妇幼保健院甲亢性心脏病患者69例(甲亢性心脏病组)、单纯甲状腺功能亢进患者69例(单纯甲亢组)、非甲亢性心脏病患者69例(非甲亢性心脏病组)和健康体检者69名(正常对照组)。收集所有研究对象的一般资料和实验室检测结果,并检测THRα1 mRNA、THRβ1 mRNA和ALCAT1。采用Logistic回归分析评估甲亢性心脏病发生的危险因素。采用相对超危险度比(RERI)、归因比(AP)和交互作用指数(SI)分析THR mRNA、ALCAT1在甲亢性心脏病发生中的交互作用。采用受试者工作特征(ROC)曲线评价THR mRNA、ALCAT1诊断甲亢性心脏病的效能。结果甲亢性心脏病组THRβ1 mRNA相对表达量和ALCAT1水平高于单纯甲亢组(P<0.001),THRα1 mRNA、THRβ1 mRNA相对表达量和ALCAT1水平高于非甲亢性心脏病组、正常对照组(P<0.001)。单纯甲亢组THRα1 mRNA、THRβ1 mRNA相对表达量和ALCAT1水平高于非甲亢性心脏病组、正常对照组(P<0.05),非甲亢性心脏病组THRα1 mRNA、THRβ1 mRNA相对表达量和ALCAT1水平高于正常对照组(P<0.05)。多因素Logistic回归分析结果显示,校正甲状腺功能亢进病程、游离三碘甲状腺原氨酸(FT_(3))、游离甲状腺素(FT_(4))、促甲状腺激素(TSH)、总三碘甲状腺原氨酸(TT_(3))、总甲状腺素(TT_(4))后,THRβ1 mRNA相对表达量和ALCAT1水平升高是甲亢性心脏病发生的危险因素[比值比(OR)值分别为3.185、3.712,95%可信区间(CI)分别为1.524~6.658、1.967~7.006,P<0.001]。THRβ1 mRNA与ALCAT1对甲亢性心脏病的发生存在正向交互作用,二者均高表达时甲亢性心脏病风险是二者均低表达时的9.000倍;二者同时高表达时甲亢性心脏病风险是其他未知因子(其OR=1)的3.148倍(RERI=3.148);协同效应是二者单独存在产生效应之和的1.855倍(SI=1.855);在二者共存的甲亢性心脏病风险中,有34.98%(AP=34.98%)由二者交互作用引起。ROC曲线分析结果显示,THRβ1 mRNA、ALCAT1单项检测和联合检测诊断甲亢性心脏病的曲线下面积(AUC)分别为0.798、0.726、0.872。结论THRβ1 mRNA、ALCAT1是甲亢性心脏病的独立危险因素,且对甲亢性心脏病的发生具有协同促进作用,二者联合检测可提升对甲亢性心脏病的诊断效能。

Objective To investigate the roles of thyroid hormone receptor(THR)mRNA and acyl-coa:lysocardiolipin acyltransferase 1(ALCAT1)in the diagnosis of hyperthyroidism heart disease.Methods A total of 69 patients with hyperthyroidism heart disease in Zhangjiakou Maternal and Child Health Hospital from February 2020 to March 2022 were enrolled as hyperthyroidism heart disease group.Totally,69 patients with hyperthyroidism were enrolled as hyperthyroidism group,69 patients with non-hyperthyroidism heart disease were enrolled as non-hyperthyroidism heart disease group,and 69 healthy subjects were enrolled as healthy control group.The general data and determination results from all the patients were collected.THRα1 mRNA,THRβ1 mRNA and ALCAT1 were determined.Logistic regression analysis was used to analyze the relationship between THR mRNA,ALCAT1 levels and hyperthyroidism heart disease.Relative excess risk due to interaction(RERI),attribution percentage(AP)and synergy index(SI)were used to analyze the interaction between THR mRNA and ALCAT1 in the occurrence of hyperthyroidism heart disease.The efficacy of THR mRNA and ALCAT1 in the diagnosis of hyperthyroidism heart disease was evaluated by receiver operating characteristic(ROC)curve.Results The relative expression level of THRβ1 mRNA and ALCAT1 level in hyperthyroidism heart disease group were higher than those in hyperthyroidism group(P<0.001),and the relative expression level of THRα1 mRNA,THRβ1 mRNA and ALCAT1 level were higher than those in non-hyperthyroidism heart disease group and healthy control group(P<0.001).The relative expression levels of THRα1 mRNA,THRβ1 mRNA and ALCAT1 level in hyperthyroidism heart disease group were higher than those in non-hyperthyroidism heart disease group and healthy control group(P<0.05),and the relative expression levels of THRα1 mRNA,THRβ1 mRNA and ALCAT1 level in non-hyperthyroidism heart disease group were higher than those in healthy control group(P<0.05).After adjusting for hyperthyroidism course,free triiodothyronine(FT_(3)),free thyroxine(FT_(4)),thyroid-stimulating hormone(TSH),total triiodothyronine(TT_(3))and total thyroxine(TT_(4)),elevated relative expression levels of THRβ1 mRNA and ALCAT1 level were risk factors for hyperthyroidism heart disease[odds ratios(OR)were 3.185 and 3.712,95%confidence intervals(CI)were 1.524-6.658 and 1.967-7.006,P<0.001].There was a positive interaction between THRβ1 mRNA and ALCAT1 on the occurrence of hyperthyroidism heart disease,and the risk of hyperthyroidism heart disease was 9.000 times when both of them were highly expressed than when both of them were lowly expressed.The risk of hyperthyroidism heart disease caused by high expression of THRβ1 mRNA and ALCAT1 was 3.148 times than that of other unknown factors(OR=1)(RERI=3.148).The synergistic effect was 1.855 times of the sum of the two effects alone(SI=1.855).The 34.98%(AP=34.98%)of the risk of hyperthyroidism heart disease was due to their interaction.The area under curve(AUC)of single and combined determinations of THRβ1 mRNA and ALCAT1 in the diagnosis of hyperthyroidism heart disease were 0.798,0.726 and 0.872,respectively.Conclusions THRβ1 mRNA and ALCAT1 are independent risk factors of hyperthyroidism heart disease,and they have synergistic effect on the occurrence of hyperthyroidism heart disease.The combined determination can improve the clinical diagnostic efficiency of hyperthyroidism heart disease.