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中华重症医学电子杂志 ›› 2021, Vol. 07 ›› Issue (03) : 208 -213. doi: 10.3877/cma.j.issn.2096-1537.2021.03.003

临床研究

MYNN rs10936599基因多态性与急性心力衰竭患者短期预后的相关性
李艳秀1, 张中文2, 刘云1, 左祥荣1, 李新立3, 曹权1,()   
  1. 1. 210029 南京医科大学第一附属医院重症医学科
    2. 210029 南京医科大学第一附属医院心血管内科
    3. 211100 南京医科大学附属江宁医院肝胆胰外科
  • 收稿日期:2021-02-07 出版日期:2021-08-28
  • 通信作者: 曹权
  • 基金资助:
    国家科技支撑计划项目课题(2011BAI11B08)

Correlation analysis of MYNN gene polymorphism in rs10936599 region and the prognosis of patients with acute heart failure

Yanxiu Li1, Zhongwen Zhang2, Yun Liu1, Xiangrong Zuo1, Xinli Li3, Quan Cao1,()   

  1. 1. Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
    2. Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, China
    3. Department of Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
  • Received:2021-02-07 Published:2021-08-28
  • Corresponding author: Quan Cao
引用本文:

李艳秀, 张中文, 刘云, 左祥荣, 李新立, 曹权. MYNN rs10936599基因多态性与急性心力衰竭患者短期预后的相关性[J]. 中华重症医学电子杂志, 2021, 07(03): 208-213.

Yanxiu Li, Zhongwen Zhang, Yun Liu, Xiangrong Zuo, Xinli Li, Quan Cao. Correlation analysis of MYNN gene polymorphism in rs10936599 region and the prognosis of patients with acute heart failure[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2021, 07(03): 208-213.

目的

探讨MYNN基因的rs10936599位点多态性与急性心力衰竭(AHF)患者预后的关系。

方法

选取2012年3月至2016年3月于南京医科大学第一附属医院心血管内科住院的AHF患者328例,采用TaqMan探针法对MYNN基因的SNP位点rs10936599(T/C)进行基因多态性检测,记录并比较不同基因型患者(TT基因型、CT基因型、CC基因型)住院期间的人口学特征、临床资料、病因和伴随疾病、住院期间治疗用药等基线资料,并对所有患者进行12个月的前瞻性随访,随访终点为全因死亡。分析rs10936599位点多态性对AHF预后的影响。

结果

(1)rs10936599基因型频率分布:TT基因型100例(占30.5%),CT基因型162例(占49.4%),CC基因型66例(占20.1%);rs10936599位点的基因型和等位基因频率在死亡患者和存活患者间比较,差异有统计学意义(χ2=9.749,P=0.0076;χ2=9.641,P=0.0019)。(2)心率、血清钾水平及住院期间地高辛和醛固酮拮抗剂使用情况在不同基因型患者间比较,差异有统计学意义(H=7.714,P=0.021;F=3.254,P=0.040);其他基线资料在不同基因型患者间比较,差异无统计学意义(P>0.05)。(3)Kaplan-Meier曲线分析显示携带等位基因C(CC/CT)的AHF患者12个月生存率较TT基因型患者明显下降,差异有统计学意义(TT vs CT,P=0.026;TT vs CC,P=0.002)。(4)进一步Cox回归分析结果显示杂合子CT基因型和纯合子CC基因型是影响AHF患者预后的独立危险因素(HR=2.10,95%CI:1.07~4.12;HR=2.96,95%CI:1.42~6.19)。

结论

MYNN基因rs10936599位点多态性与AHF患者预后有关,CC和CT基因型是预测AHF患者12个月不良预后的独立危险因素。

Objective

To investigate the relationship between the rs10936599 polymorphism of MYNN gene and the prognosis of patients with acute heart failure (AHF).

Methods

A total of 328 hospitalized patients with AHF from 2012 to 2016 were prospectively enrolled. Patients were followed up to 12 months. The primary outcome was all-cause mortality. The SNP locus rs10936599 (T/C) of the MYNN gene were analyzed by TaqMan method. Baseline characteristics were compared between groups which divided based on the different genotypes (TT genotype, CT genotype, CC genotype). Cox Regression analysis were used to identify the association between rs10936599 and outcome.

Results

(1) Frequency distribution of rs10936599 genotype: there were 100 cases of homozygous TT genotype (30.5%), 162 cases of heterozygous CT genotype (49.4%), 66 cases of mutation homozygous CC genotype (20.1%); AHF patients with different genotypes had a significant difference of 12-month mortality (χ2=9.749, P=0.0076; χ2=9.641, P=0.0019). (2) Baseline characteristics comparison among different genotypes showed a significant difference of the heart rate, serum potassium, and medications of Digoxin and Aldosterone antagonist during hospitalization (H=7.714, P=0.021; F=3.254, P=0.040). (3) Kaplan-Meier analysis showed the 12-month survival rate of patients with AHF carrying allele C (CC/CT) was significantly lower than that of patients with TT genotype (TT vs CT, P= 0.026; TT vs CC, P=0.002). (4) Cox regression analysis showed that homozygous CT genotype and heterozygous CC genotype were independent risk factors for the death of patients with acute heart failure (HR=2.10, 95%CI: 1.07-4.12; HR=2.96, 95%CI: 1.42-6.19).

Conclusion

MYNN rs10936599 gene polymorphisms are associated with the 12-month mortality of patients with AHF. CC and CT genotype are independent risk factors of 12-month mortality of AHF.

表1 急性心力衰竭患者的基因型和等位基因频率分布比较[例(%)]
表2 不同基因型患者一般资料和辅助检查比较
指标 TT(100例) CT(162例) CC(66例) 统计值 P
年龄(岁,
x¯
±s
60.00±15.62 59.54±16.83 64.02±15.62 F=1.877 0.155
性别(例,女/男) 34/66 53/109 24/42 χ2=0.280 0.869
吸烟史[例(%)] 34(34.0) 69(42.6) 23(34.8) χ2=2.374 0.305
体质量指数(kg/m2
x¯
±s
23.95±4.37 24.10±4.54 25.09±4.54 F=1.205 0.301
收缩压(mmHg,
x¯
±s
127±25 125±21 124±19 F=0.458 0.633
舒张压(mmHg,
x¯
±s
79±17 79±15 76±13 F=1.206 0.301
心率[次/分,MQ25Q75)] 83(71,102) 88(76,102) 80(64,93) H=7.714 0.021a
血钾(mmol/L,
x¯
±s
3.88±0.50 4.03±0.50 4.05±0.50 F=3.254 0.040
血钠(mmol/L,
x¯
±s
140.0±4.0 140.0±4.2 140.0±3.9 F=0.275 0.759
血钙(mmol/L,
x¯
±s
2.25±0.14 2.26±0.14 2.25±0.15 F=0.072 0.931
丙氨酸氨基转移酶[U/L,MQ25Q75)] 28.70(17.95,51.05) 32.85(20.28,70.68) 24.85(17.60,45.85) H=1.543 0.462a
天冬氨酸氨基转移酶[U/L,MQ25Q75)] 31.10(21.48,54.03) 33.90(22.15,59.95) 26.35(22.73,35.10) H=3.663 0.160a
血肌酐(μmol/L,
x¯
±s
102.0±61.4 103.9±68.9 95.4±40.5 F=0.439 0.645
红细胞分布宽度(%,
x¯
±s
15.52±8.18 14.70±1.86 14.71±1.50 F=1.020 0.362
D二聚体(mg/L,
x¯
±s
1.54±2.81 1.95±4.64 1.80±3.15 F=0.344 0.709
NT-proBNP(ng/L,
x¯
±s
3090±3493 3725±4535 3522±4922 F=0.626 0.536
肌钙蛋白T[ng/L,MQ25Q75)] 0.05(0.05,0.66) 0.05(0.05,2.38) 0.05(0.05,0.16) H=3.664 0.160a
CK-MB[U/L,MQ25Q75)] 12.55(9.40,20.58) 14.35(11.05,20.93) 12.85(9.18,19.25) H=2.092 0.351a
LVEF(%,
x¯
±s
42.45±14.43 42.29±15.89 42.42±14.71 F=0.025 0.975
纽约心功能分级[例(%)] χ2=3.641 0.457

2级

19(19.0) 21(13.0) 10(15.2)

3级

52(52.0) 89(54.9) 41(62.1)

4级

29(29.0) 52(32.1) 15(22.7)
表3 不同基因型患者病因和伴随疾病情况比较[例(%)]
表4 不同基因型患者住院期间治疗情况比较[例(%)]
图1 不同基因型患者的生存曲线
表5 不同基因型患者死亡危险因素的Cox回归分析
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