3q26 rs12696304基因多态性与中国南方汉族老年人群急性心力衰竭患者一年预后间的关系研究

doi:10.16150/j.1671-2870.2020.06.004

摘要/Abstract

摘要：

目的： 研究3q26 rs12696304基因多态性与急性心力衰竭（急性心衰）患者1年预后间的关系。方法： 2012年3月至2016年4月间,收集南京医科大学第一附属医院收治的336例急性心衰患者（≥60岁）。采用TaqMan荧光探针实时定量聚合酶链式反应（polymerase chain reaction,PCR）技术法检测患者外周血DNA中的3q26 rs12696304基因多态性, 采用Kaplan-Meier法和log-rank检验,分析不同遗传模型下各基因型急性心衰患者1年的生存率;采用多因素Cox回归分析探讨3q26 rs12696304基因多态性与急性心衰患者1年预后间的相关性。结果： 在共显性遗传模型中,携带杂合子CG基因型的急性心衰患者其1年生存率（74.8%）比携带纯合子GG基因型患者（85.4%）低（CG比GG,P=0.027）;在显性遗传模型中,携带CG+CC基因型急性心衰患者其生存率（74.9%）较纯合子GG基因型患者生存率（85.4%）明显下降（P=0.023）,CC+CG基因型急性心衰患者发生死亡的风险系数是GG基因型患者的2.45倍[风险比（hazard ratio,HR）=2.45,95%CI为1.24~4.84,P=0.010]。结论： 检测3q26 rs12696304基因多态性可能有助于评估中国南方汉族老年人群中急性心衰患者1年的预后情况。

关键词: 单核苷酸多态性, 3q26 rs12696304, 急性心力衰竭, 预后

Abstract:

Objective: To investigate the correlation between the gene polymorphism of rs12696304 in chromosome 3q26 and 1-year survival rate in the patients with acute heart failure (AHF). Methods: A total of 336 elderly patients of Han population in South China (aged≥60 years) with AHF were enrolled during March 2012 and April 2016. DNA of each patient was extracted from peripheral blood, and the gene polymorphism of rs12696304 was analyzed by real-time fluorescence quantitative PCR with TaqMan probe. One-year survival rate was compared between the patients with diffe-rent gene typing in multiple genetic models using Kaplan-Meier and log-rank test. The Cox regression analysis was used to assess relation between the gene polymorphism of rs12696304 and 1-year survival rate in the patients with AHF. Results: In the co-dominant genetic model, the 1-year survival rate of the AHF patients carrying heterozygous CG genotypes was lower than that of patients carrying wild homozygous GG genotypes (74.8% vs 85.4%, P=0.027). In the dominant genetic model, 1-year survival rate of the AHF patients carrying CG+CC genotype was significantly lower than that of patients carrying the wild homozygous GG genotype (74.9% vs 85.4%, P=0.023). Further Cox regression analysis showed that the risk of 1-year death in the AHF patients carrying CG+CC genotype was 2.45 times of that in the patients with GG genotype (HR=2.45, 95%CI: 1.22-4.95, P=0.012) after adjustment with the relevant variables in codominant model, and in the dominant model, the risk of 1-year death was also 2.45 times of that in patients with GG genotype (HR=2.45, 95%CI: 1.24-4.84, P=0.010). Conclusions: The gene polymorphisms of rs12696304 located in chromosome 3q26 region may be associated with the 1-year prognosis in the patients with AHF.

Key words: Single nucleotide polymorphism, 3q26 rs12696304, Acute heart failure, Prognosis

中图分类号:

R541.6

张中文, 左祥荣, 郑绪辉, 曹权, 李新立, 李艳秀. 3q26 rs12696304基因多态性与中国南方汉族老年人群急性心力衰竭患者一年预后间的关系研究[J]. 诊断学理论与实践, 2020, 19(06): 565-571.

ZHANG Zhongwen, ZUO Xiangrong, ZHENG Xuhui, CAO Quan, Li Xinli, LI Yanxiu. Correlation between gene polymorphism of chromosome 3q26 rs12696304 and 1-year survival rate after acute heart failure in an elderly Han population in South China[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(06): 565-571.

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组别	基因型					等位基因
组别	GG	CG	CC	P值^a)	P_HW值	G	C	P值^b)
例数	157(46.7)	143(42.6)	36(10.7)	-	0.687 1	457(68.0)	215(32.0)	-
死亡	23(14.6)	36(25.2)	9(25.0)	0.057 9	0.383 5	82(17.9)	54(25.1)	0.030 9
存活	134(85.4)	107(74.8)	27(75.0)		0.412 4	375(82.1)	161(74.9)

项目	GG基因型(n=157)	CG基因型(n=143)	CC基因型(n=36)	P值
年龄(岁)	60.02±15.85	60.22±16.23	63.86±17.29	0.421
性别(女/男)	56/101	45/98	13/23	0.699
体质量指数 (kg/m²)	23.74±4.53	24.27±4.09	25.95±5.44^a)	0.057
心率(次/min)	88±24	86±21	80±17^a)	0.130
收缩压(mmHg)	127±24	124±22	129±20	0.264
舒张压(mmHg)	79±16	78±14	80±18	0.604
谷丙转氨酶(U/L)	31.1(18.5, 67.2)	31.7(20.8, 57.9)	24.6(15.7, 46.1)	0.219^b)
谷草转氨酶(U/L)	32.8(21.9, 56.3)	30.9(22.6, 49.9)	26.0(21.3, 33.4)	0.081^b)
血肌酐(μmol/L)	101.0±59.5	103.8±66.9	95.0±42.7	0.736
血尿素氮(mmol/L)	8.08±3.72	8.72±4.88	8.50±4.68	0.439
血钾(mmol/L)	3.97±0.50	4.01±0.51	4.05±0.53	0.646
血钠(mmol/L)	140.2(137.0, 142.0)	140.4(137.2, 142.9)	140.3(137.8, 140.3)	0.810^b)
血钙(mmol/L)	2.25±0.13	2.26±0.15	2.23±0.13	0.495
D-二聚体(mg/L)	1.76±3.7	1.99±4.26	1.05±1.57	0.427
NT-proBNP(ng/L)	3 234±4 019	3 782±4 806	3 012±2 899	0.469
肌钙蛋白T(ng/L)	0.05(0.05, 0.88)	0.05(0.05, 2.00)	0.05(0.05, 0.16)	0.410^b)
肌酸激酶同工酶(U/L)	13.95(9.83, 22.38)	13.20(9.95, 19.50)	16.20(10.60, 19.00)	0.926^b)

项目	GG基因型(n=157)	CG基因型(n=143)	CC基因型(n=36)	P值
NYHA心功能分级				0.024
2级	30(19.1)	14(9.8)	8(22.2)	0.034
3级	82(52.2)	79(55.2)	23(63.9)	0.458
4级	45(28.7)	50(35.0)	5(13.9)	0.038
主要超声心动图指标
左心室舒张末期内径 (mm)	62.01±12.95	61.92±11.57	59.56±13.14	0.547
左心室收缩末期内径 (mm)	49.34±14.77	49.48±12.75	45.69±14.15	0.319
肺动脉收缩压(mmHg)	43.85±17.73	43.78±16.41	46.25±24.08	0.770
左心室射血分数 (%)	42.55±15.60	41.20±13.35	45.66±15.82	0.262
病因
缺血性心脏病	36(22.9)	41(28.7)	6(16.7)	0.282
心肌病	66(42.0)	61(42.7)	10(27.8)	0.252
心脏瓣膜病	42(26.8)	34(23.8)	11(30.6)	0.647
肺源性心脏病	12(7.6)	7(4.9)	4(11.1)	0.306
房颤	64(40.8)	52(36.4)	9(25.0)	0.198
伴发疾病
高血压病	80(51.0)	72(50.3)	20(55.6)	0.868
糖尿病	29(18.5)	42(29.4)	11(30.6)	0.058
吸烟史	50(31.8)	64(44.8)	15(41.7)	0.062

项目	GG基因型 (n=157)	CG基因型 (n=143)	CC基因型 (n=36)	P值
静脉利尿剂	93(59.2)	88(61.5)	25(69.4)	0.524
口服利尿剂	155(98.7)	133(93.0)	33(91.7)	0.014
襻利尿剂	150(95.5)	134(93.7)	34(94.3)	0.513
螺内酯	147(93.6)	133(93.0)	30(83.3)	0.116
地高辛	81(51.6)	62(43.4)	8(22.2)	0.005
血管扩张剂	71(45.2)	65(45.5)	13(36.1)	0.574
ACEI或ARB	129(82.2)	117(81.8)	27(75.0)	0.595
β受体阻滞剂	123(78.3)	120(83.9)	31(86.1)	0.372
左西孟旦	9(5.8)	12(8.4)	9(25.0)	0.004
冻干重组人脑钠肽	7(4.5)	9(6.3)	4(11.1)	0.306
多巴胺	36(22.9)	29(20.4)	6(16.7)	0.679
阿司匹林	70(44.6)	62(43.4)	9(25.0)	0.090
抗凝药	72(45.9)	72(50.3)	13(36.1)	0.297

项目	显性模型			隐性模型
项目	CG+CC(n=179)	GG(n=157)	P值	CC(n=36)	GG+CG(n=300)	P值
年龄 (岁)	60.96±16.46	60.02±15.85	0.597	63.86±17.29	60.12±16.01	0.189
性别 (女/男)	58/121	56/101	0.564	13/23	101/199	0.852
体质量指数 (kg/m²)	24.60±4.41	23.74±4.53	0.122	25.95±5.44	24.01±4.31	0.027
心率 (次/min)	85±20	88±24	0.233	80±17	87±22	0.053
收缩压 (mmHg)	125±22	127±24	0.401	129±20	125±23	0.294
舒张压 (mmHg)	78±15	79±16	0.696	80±18	78±15	0.454
谷氨酸转氨酶 (U/L)	28.4(19.0, 47.8)	31.1(18.5, 67.2)	0.919	24.6(15.7, 46.1)	30.4(19.9, 58.7)	0.093
谷草转氨酶 (U/L)	28.4(22.1, 43.7)	32.8(21.9, 56.3)	0.983	26.0(21.3, 33.4)	31.0(22.3, 51.1)	0.033
血肌酐 (μmol/L)	102.0±62.8	101.0±59.5	0.886	95.0±42.7	102.3±63.1	0.496
血尿素氮 (mmol/L)	8.68±4.83	8.08±3.72	0.210	8.50±4.68	8.39±4.32	0.881
血钾 (mmol/L)	4.01±0.51	3.97±0.50	0.404	4.05±0.53	3.99±0.51	0.505
血钠 (mmol/L)	140.4(137.4, 142.7)	140.2(137.0, 142.0)	0.860	140.3(137.8, 140.3)	140.3(137.2, 42.5)	0.594
血钙 (mmol/L)	2.25±0.15	2.25±0.13	0.982	2.23±0.13	2.26±0.14	0.265
D-二聚体 (mg/L)	1.79±3.88	1.76±3.7	0.928	1.05±1.57	1.87±3.99	0.229
NT-proBNP (ng/L)	3 634±4 506	3 234±4 019	0.409	3 012±2 899	3 497±4 415	0.544
肌钙蛋白T (ng/L)	0.05(0.05, 0.29)	0.05(0.05, 0.88)	0.891	0.05(0.05, 0.16)	0.05(0.05, 0.96)	0.195
肌酸激酶同工酶 (U/L)	13.15(9.93, 19.00)	13.95(9.83, 22.38)	0.944	16.20(10.60, 19.00)	13.1(9.61, 19.9)	0.733