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

doi:10.3877/cma.j.issn.2096-1537.2021.03.003

Abstract

Abstract:

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.

Key words: MYNN gene, rs10936599, Acute heart failure, Prognosis

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.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2021.03.003

https://icu.cma-cmc.com.cn/EN/Y2021/V07/I03/208

Figures/Tables 6

结局	基因型			等位基因
结局	TT（100例）	CT（162例）	CC（66例）	T（362例）	C（294例）
死亡	11（11.0）	36（22.2）	20（30.3）	58（16.0）	76（25.9）
存活	89（89.0）	126（77.8）	46（69.7）	304（84.0）	218（74.1）
χ²值	9.479			9.641
P值	0.0076			0.0019

指标	TT（100例）	CT（162例）	CC（66例）	统计值	P值
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，M（Q₂₅，Q₇₅）］	83（71，102）	88（76，102）	80（64，93）	H=7.714	0.021^a
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，M（Q₂₅，Q₇₅）］	28.70（17.95，51.05）	32.85（20.28，70.68）	24.85（17.60，45.85）	H=1.543	0.462^a
天冬氨酸氨基转移酶［U/L，M（Q₂₅，Q₇₅）］	31.10（21.48，54.03）	33.90（22.15，59.95）	26.35（22.73，35.10）	H=3.663	0.160^a
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，M（Q₂₅，Q₇₅）］	0.05（0.05，0.66）	0.05（0.05，2.38）	0.05（0.05，0.16）	H=3.664	0.160^a
CK-MB［U/L，M（Q₂₅，Q₇₅）］	12.55（9.40，20.58）	14.35（11.05，20.93）	12.85（9.18，19.25）	H=2.092	0.351^a
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）

指标	TT（100例）	CT（162例）	CC（66例）	统计值	P值
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，M（Q₂₅，Q₇₅）］	83（71，102）	88（76，102）	80（64，93）	H=7.714	0.021^a
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，M（Q₂₅，Q₇₅）］	28.70（17.95，51.05）	32.85（20.28，70.68）	24.85（17.60，45.85）	H=1.543	0.462^a
天冬氨酸氨基转移酶［U/L，M（Q₂₅，Q₇₅）］	31.10（21.48，54.03）	33.90（22.15，59.95）	26.35（22.73，35.10）	H=3.663	0.160^a
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，M（Q₂₅，Q₇₅）］	0.05（0.05，0.66）	0.05（0.05，2.38）	0.05（0.05，0.16）	H=3.664	0.160^a
CK-MB［U/L，M（Q₂₅，Q₇₅）］	12.55（9.40，20.58）	14.35（11.05，20.93）	12.85（9.18，19.25）	H=2.092	0.351^a
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）

疾病	TT（100例）	CT（162例）	CC（66例）	χ²值	P值
缺血性心脏病	25（25.0）	42（25.9）	13（19.7）	1.016	0.602
心肌病	37（37.0）	70（43.2）	24（36.4）	1.434	0.488
心脏瓣膜病	29（29.0）	36（22.2）	22（33.3）	3.423	0.181
肺源性心脏病	10（10.0）	9（5.6）	4（6.1）	1.920	0.447
房颤	38（38.0）	63（38.9）	22（33.3）	0.633	0.729
高血压病	53（53.0）	82（50.6）	32（48.5）	0.336	0.846
糖尿病	24（24.0）	36（22.2）	18（27.3）	0.664	0.715

治疗	TT（100例）	CT（162例）	CC（66例）	χ²值	P值
左西孟旦	5（5.1）	14（8.6）	10（15.2）	4.783	0.084
重组人脑利钠肽	4（4.0）	11（6.8）	5（7.6）	1.156	0.561
多巴胺	22（22.0）	35（21.7）	13（19.7）	0.142	0.952
地高辛	55（55.0）	72（44.4）	20（30.3）	9.858	0.007
袢利尿剂	96（96.0）	156（96.3）	58（87.9）	5.949	0.051
醛固酮拮抗剂	93（93.0）	155（95.7）	55（83.3）	10.230	0.006
β受体阻滞剂	82（82.0）	129（79.6）	57（86.4）	1.431	0.489
ACEI/ARB	85（85.0）	131（80.9）	52（78.8）	1.179	0.555
抗血小板药	42（42.0）	74（45.7）	20（30.3）	4.585	0.101
抗凝药	45（45.0）	80（49.4）	31（47.0）	0.488	0.784

变量	B	SE	Wald χ²	HR（95%CI）	P值
TT	-	-	8.40	-	0.015
CT	0.74	0.35	4.61	2.10（1.07~4.12）	0.032
CC	1.09	0.38	8.38	2.96（1.42~6.19）	0.004

References 32

1	Davidsohn N, Pezone M, Vernet A, et al. A single combination gene therapy treats multiple age-related diseases [J]. Proc Natl Acad Sci USA, 2019, 116(47): 23505-23511.
2	de Almeida AJPO, de Almeida Rezende MS, Dantas SH, et al. Unveiling the role of inflammation and oxidative stress on age-related cardiovascular diseases [J]. Oxid Med Cell Longev, 2020, 2020: 1954398.
3	Kurmani S, Squire I. Acute heart failure: definition, classification and epidemiology [J]. Curr Heart Fail Rep, 2017, 14(5): 385-392.
4	Berglund K, Reynolds CA, Ploner A,et al. Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk [J]. Aging (Albany NY), 2016, 8(7): 1398-1415.
5	Herrmann M, Pusceddu I, März W, et al. Telomere biology and age-related diseases [J]. Clin Chem Lab Med, 2018, 56(8): 1210-1222.
6	Fasching CL. Telomere length measurement as a clinical biomarker of aging and disease [J]. Crit Rev Clin Lab Sci, 2018, 55(7): 443-465.
7	Li C, Stoma S, Lotta LA, et al. Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length [J]. Am J Hum Genet, 2020, 106(3): 389-404.
8	Prescott J, Kraft P, Chasman DI, et al. Genome-wide association study of relative telomere length [J]. PLoS One, 2011, 6(5): e19635.
9	Delgado DA, Zhang C, Chen LS, et al. Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal [J]. J Med Genet, 2018, 55(1): 64-71.
10	中华医学会心血管病学分会, 中华心血管病杂志编辑委员会. 中国心力衰竭诊断和治疗指南2014 [J]. 中华心血管病杂志, 2014, 42(2): 98-122.
11	Shi YY, He L. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci [J]. Cell Res, 2005, 15(2): 97-98.
12	Greenberg B. Gene therapy for heart failure [J]. Trends Cardiovasc Med, 2017, 27(3): 216-222.
13	Fish KM, Ishikawa K. Advances in gene therapy for heart failure [J]. Discov Med, 2015, 19(105): 285-291.
14	Morales A, Hershberger R. Clinical application of genetic testing in heart failure [J]. Curr Heart Fail Rep, 2017, 14(6): 543-553.
15	Ozaki K. Genetic background of heart failure: SNP association study for heart failure and the underlying diseases [J]. Rinsho Byori, 2013, 61(2): 167-175.
16	Bahramali E, Firouzabadi N, Rajabi M, et al. Association of renin-angiotensin-aldosterone system gene polymorphisms with left ventricular hypertrophy in patients with heart failure with preserved ejection fraction: A case-control study [J]. Clin Exp Hypertens, 2017, 39(4): 371-376.
17	白强, 胡紫薇, 兰晓栋, 等.血管紧张素转换酶基因多态性与我国慢性心力衰竭易感性分析 [J].中国循证心血管医学杂志, 2020, 12(11): 1311-1315.
18	El-Mahdy RI, Saleem TH, Essam OM, et al. Functional variants in the promoter region of macrophage migration inhibitory factor rs755622 gene (MIF G173C) among patients with heart failure: Association with echocardiographic indices and disease severity [J]. Heart Lung, 2021, 50(1): 92-100.
19	Wang Y, Zhang Y, An T, et al. ErbB4 gene polymorphism is associated with the risk and prognosis of congestive heart failure in a Northern Han Chinese population [J]. J Card Fail, 2016, 22(9): 700-709.
20	徐万忠, 白艳丽, 王晓麒. 白细胞介素6基因多态性对老年严重心力衰竭患者预后的预测作用 [J]. 中华老年心脑血管病杂志, 2020, 22(7): 722-724.
21	Sandip C, Tan L, Huang J, et al. Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure [J]. Medicine (Baltimore), 2016, 95(27): e4105.
22	Zhang G, Dou L, Chen Y. Association of long-chain non-coding RNA MHRT gene single nucleotide polymorphism with risk and prognosis of chronic heart failure [J]. Medicine (Baltimore), 2020, 99(29): e19703.
23	Kao DP, Stevens LM, Hinterberg MA, et al. Phenotype-specific association of single-nucleotide polymorphisms with heart failure and preserved ejection fraction: a genome-wide association analysis of the cardiovascular health study [J]. J Cardiovasc Transl Res, 2017, 10(3): 285-294.
24	Hao Y, Chen Y. Vitamin D levels and vitamin D receptor variants are associated with chronic heart failure in Chinese patients [J]. J Clin Lab Anal, 2019, 33(4): e22847.
25	He HR, Li YJ, He GH, et al. The adenosine deaminase gene polymorphism is associated with chronic heart failure risk in Chinese [J]. Int J Mol Sci, 2014, 15(9): 15259-15271.
26	Do SK, Yoo SS, Choi YY, et al. Replication of the results of genome-wide and candidate gene association studies on telomere length in a Korean population [J]. Korean J Intern Med, 2015, 30(5): 719-726.
27	Wang M, Chu H, Lv Q, et al. Cumulative effect of genome-wide association study-identified genetic variants for bladder cancer [J]. Int J Cancer, 2014, 135(11): 2653-2660.
28	Chubb D, Weinhold N, Broderick P, et al. Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk [J]. Nat Genet, 2013, 45(10): 1221-1225.
29	Ding H, Yan F, Zhou LL, et al. Association between previously identified loci affecting telomere length and coronary heart disease (CHD) in Han Chinese population [J]. Clin Interv Aging, 2014, 9: 857-861.
30	Zhang S, Ji G, Liang Y,et al. Polymorphisms in telomere length associated TERC and TERT predispose for ischemic stroke in a Chinese Han population [J]. Sci Rep, 2017, 7: 40151.
31	Liu P, Zhang Y, Ma L. Telomere length and associated factors in older adults with hypertension [J]. J Int Med Res, 2019, 47(11): 5465-5474.
32	赵连泽, 安友仲. 端粒长度与冠心病危险因素的研究进展 [J]. 中国循环杂志, 2018, 33(5): 507-509.

[1]	Kang Ying, Canying Yang, Fengzhen Liu, Lili Chen, Yanna Liu. Prognostic value of left ventricular myocardial strain in asymptomatic patients with severe aortic stenosis [J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(06): 581-587.
[2]	Xiaoli Yi, Shasha Hu, Yan Zhang. Impact of HER-2 low expression on response of neoadjuvant chemotherapy and prognosis in breast cancer patients [J]. Chinese Journal of Breast Disease(Electronic Edition), 2023, 17(06): 340-346.
[3]	Jie Shi, Yuntao Li, Haiyan Gao. Prognosis of node-positive luminal A breast cancer patients with neoadjuvant and adjuvant chemotherapy and influencing factors [J]. Chinese Journal of Breast Disease(Electronic Edition), 2023, 17(06): 353-361.
[4]	Siping Zhang, Wei Liu, Pengcheng Ma. Therapeutic effects of lower extremity mild varus alignment after total knee arthroplasty [J]. Chinese Journal of Joint Surgery(Electronic Edition), 2023, 17(06): 808-817.
[5]	Yuezhou Li, Kongxi Zhang, Xiaohong Li, Zhonghua Shang. Prognostic significance of PUM in gastric carcinoma based on bioinformatics analysis [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(06): 426-432.
[6]	Jun Zhang, Zai Luo, Mingyu Duan, Zhengjun Qiu, Chen Huang. Research progress of prognostic prediction models for gastric cancer [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(06): 456-461.
[7]	Qian Yang, Cuifang Li, Wanqiu Zhang. Analysis of short-term and long-term prognosis and influencing factors of primary liver cancer with spontaneous ruptured hemorrhage after emergency TACE surgery [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(01): 33-36.
[8]	Yansong Li, Huimin Feng, Mingchao Liu, Zepeng Liu, Qiuxia Jiang. Expression and clinical significance of STIP1 in triple negative breast cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(01): 52-56.
[9]	Zhenjian Jiang, Ming Jiang, Dali Huang. The expression and prognostic value of TK1 and Ki67 proteins in differentiated thyroid carcinoma [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 623-626.
[10]	Qingyan Yan, Xiaomei Yong, Hong Luo, Min Du. Prognostic factors and survival analysis of multicenter elderly patients with metastatic breast cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 636-638.
[11]	Xin Lu, Jiayi Xu, Yang Liu, Qin Yang, Wenwen Ju, Yinglong Xu. Comparison of the effects of early LC and PTCD continuous LC on liver function and prognosis of patients with acute cholecystitis [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 648-650.
[12]	Yanjun Lu, Jian Ma, Pengyu Bai, Linghong Guo, Haiyi Liu, Bo Jiang, Wenqi Bai, Yixun Zhang. Clinical effect of Nano-carbon on 253 groups of lymph node dissection in laparoscopic radical resection of rectal cancer [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2023, 12(06): 473-477.
[13]	Yongsheng Li, Jiahe Sun, Shuwei Guo, Yikang Lu, Hongzhou Liu. Short-term postoperative complications and their influencing factors in elderly patients with colorectal cancer [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(9): 962-967.
[14]	Jun Wang, Kunpeng Liu, Lan Yao, Hua Zhang, Yue Wei, Libin Suo, Jun Chen, chengli Miao, Chenghua Luo. Retrospective analysis of anesthesia management of massive transfusion patients undergoing retroperitoneal tumor resection [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(08): 844-849.
[15]	Libin Suo, Kunpeng Liu, Lan Yao, Hua Zhang, Yue Wei, Jun Wang, Jun Chen, Chengli Miao, Chenghua Luo. Key points of anesthesia management and prognostic factors in patients undergoing primary retroperitoneal paraganglioma resection [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(07): 771-776.

Please choose a citation manager

Content to export