基因检测指导下的个体化用药在农村高血压患者管理中的效果评价

倪小丽; 汤权琪; 邹仕贵; 李伦兰; 张胜权

doi:10.16462/j.cnki.zhjbkz.2019.10.024

基因检测指导下的个体化用药在农村高血压患者管理中的效果评价

doi: 10.16462/j.cnki.zhjbkz.2019.10.024

倪小丽^{1, 2},
汤权琪³,
邹仕贵⁴,
李伦兰^1, ,,
张胜权²

1.
230000 合肥, 安徽医科大学第一附属医院护理部
2.
231500 合肥, 庐江县人民医院心内科
3.
231500 合肥, 庐江县人民医院肿瘤科
4.
231500 合肥, 庐江县人民医院护理部
5.
230000 合肥, 安徽医科大学基础医学院教研室

基金项目:

安徽省高校自然科学研究项目 KJ2017A195

详细信息

通讯作者:
李伦兰, E-mail: lilunlan@aliyun.com

中图分类号: R248.1
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- 被引次数: 0
出版历程
- 收稿日期: 2019-06-17
- 修回日期: 2019-09-03
- 刊出日期: 2019-10-10

Evaluation of individualized medication under the guidance of genetic testing in the management of hypertension patients in rural areas

1.
Nursing Department, Anhui First Affiliated Hospital of Anhui Medical University, Hefei 230000, China
2.
Department of Cardiology, People's Hospital of Lujiang County, Anhui Medical University, Hefei 231500, China
3.
Department of Oncology, People's Hospital of Lujiang County, Hefei 231500, China
4.
Nursing Department, People's Hospital of Lujiang County, Hefei 231500, China
5.
Department of Basic Medical Sciences, Anhui Medical University, Hefei 230000, China

Funds:

Natural Science Research Project of Anhui Province KJ2017A195

More Information

Corresponding author: LI Lun-lan, E-mail: lilunlan@aliyun.com

摘要

摘要: 目的研究基因检测指导用药与家庭医生相结合的管理模式在农村原发性高血压患者中的应用成效。方法将安徽农村209例原发性高血压患者分为试验组（105人）和对照组（104人）。在家庭医生签约模式下，对试验组结合个体化用药基因检测结果指导用药，对照组实施常规用药。经6个月干预，观察两组患者的治疗依从性、药物不良反应率、血压值和体重指数（body mass index，BMI）、空腹血糖（fasting blood glucose，FBG）、血清总胆固醇（total cholesterol，TC）和甘油三酯（triglycerides，TG）的变化。结果干预6个月后，试验组患者的服药依从性明显高于对照组，血压值和药物不良反应率明显低于对照组；干预3个月后，两组患者的BMI、FBG、TC和TG均无明显下降，干预6个月后，试验组FBG、TC和TG均有明显下降，对照组仅FBG值有明显下降，两组患者的BMI值均无明显变化。结论家庭医生签约服务模式下，基因检测指导用药能提高原发性高血压患者的服药依从性，降低药物不良反应率，提高治疗效率。
- 基因检测 /
- 家庭医生签约服务 /
- 农村地区 /
- 原发性高血压
Abstract: Objective This study combined genotyping with family doctors' contracting model to assess the application of precision medicine in rural patients with essential hypertension. Methods In this study, 209 hypertensive patients from 3 villages in Lujiang County, Hefei City, Anhui Province were selected as subjects and randomly divided into experimental group(n=105) and control group(n=104). The medication regimen of observation group was guided by genetic testing for gene sensitivity to antihypertensive drugs, and the control group was implemented routine pharmacy. All the patients were managed by family doctors. Adverse drug reaction rate, treatment compliance, blood pressure, body mass index (BMI), fasting blood glucose (FBG), cholesterol (TC), and triglycerides (TG) of the two groups were analyzed, respectively, during the 6-month intervention. Results After 6-month of intervention, the medication compliance of the experimental group were significantly higher than that of the control group, and the blood pressure and adverse drug reaction rate were significantly lower than that of the control group. After 3 months of intervention, there was no significant decrease in BMI, FBG, TC and TG in the two groups. After 6 months of intervention, the FBG, TC and TG of the experimental group were significantly decreased, while only the FBG value of the control group was significantly decreased. There were no significant changes in body mass index (BMI) values in both groups. Conclusions Individualized medication guided by genotyping can improve the treatment compliance, reduce the adverse drug reaction rate, and improve the treatment efficiency of patients with essential hypertension.
- Gene test /
- Family doctors contracted services /
- Rural areas /
- Essential hypertension

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表 1 高血压个体化用药基因检测位点

Table 1. Individualized drug detection site for hypertension

药物分类	药物名称	相关基因	检测位点
ACEI	依那普利	NR3C2	rs5186
	赖诺普利	ACE	rs4291
	卡托普利	ACE2	rs2106809
	培哚普利	AGTR1	rs1801253
	咪达普利/贝那普利	CYP11B2	rs1801253
ARB	雷米普利	ACE	rs4344
	氯沙坦厄贝沙坦	CYP2C9	rs1801253
	替米沙坦	GNB3	rs5186
	坎地沙坦	CYP11B2	rs1801253
	奥美沙坦酯	SLCO1B1	rs5186
β受体阻滞剂	阿替洛尔/比索洛尔	ADRB1	rs1801253
	美托洛尔/美托洛尔缓释片/卡维地洛	CYP2D6	rs1065852
CCB	氨氯地平/左旋氨氯地平	CYP3A5	rs776746
		ACE	rs4291
	硝苯地平/硝苯地平缓释片	ADRA1A	rs2106809
	硝苯地平控释片/尼群地平	AGTR1	rs1801253
利尿剂	氢氯噻嗪	YEATS4	rs7297610
		NEDD4L	rs5186

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表 2 两组患者的一般人口学基本信息比较[n(%)]

Table 2. Comparison of general basic information between the two groups[n(%)]

变量	试验组(n=105)	对照组(n=104)	χ²值	P值
性别			0.249	0.618
男	58(55.24)	61(58.65)
女	47(44.76)	43(41.35)
年龄(岁)			0.402	0.818
35~	17(16.19)	15(14.42)
56~	54(51.43)	58(55.77)
≥76	34(32.38)	31(28.81)
婚姻状况			0.119	0.731
在婚	87(82.86)	88(84.62)
其他	18(17.14)	16(15.38)
文化程度			1.570	0.666
小学及以下	16(15.24)	17(16.35)
初中	47(44.76)	49(47.12)
高中或中专	31(29.52)	28(26.92)
大专及以上	11(10.48)	10(9.62)
月均收入(元)			0.390	0.823
< 500	20(19.05)	23(22.12)
500~	58(55.24)	57(54.80)
≥1 000	27(25.71)	24(23.08)
患病年限(年)			1.552	0.460
< 5	53(50.48)	49(47.11)
5~	41(39.05)	38(36.54)
≥10	11(10.47)	17(16.35)
高血压分级			0.822	0.884
低危	9(8.57)	9(8.65)
中危	55(52.38)	51(49.04)
高危	34(32.38)	39(37.50)
很高危	7(6.67)	5(4.81)
高血压控制率	21(20.00)	22(21.15)	0.043	0.866

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表 3 试验组患者15个相关基因位点基因型及基因频率分布

Table 3. The allele frequencies for the 15 related SNPs in patients of the experimental group

碱基位点	相关基因型 /n(%)	基因
碱基位点	相关基因型 /n(%)	野生型	杂合变异	纯合变异
rs4291	ACE	AA/30(28.57)	AT/58(55.24)	TT/17(16.19)
rs1057910	CYP2C9	AA/90(85.71)	AC/9(8.57)	CC/6(5.71)
rs1065852	CYP2D6	AA/25(23.81)	AG/64(60.95)	GG/16(15.24)
rs1801253	ADRB1	CC/44(41.90)	CG/49(46.67)	GG/12(11.43)
rs1799998	CYP11B2	AA/54(51.43)	AG/48(45.71)	GG/3(2.86)
rs4149601	NEDD4L	GG/66(62.86)	GA/33(31.43)	AA/6(5.71)
rs2106809	ACE2	AA/42(40.00)	GA/24(22.86)	GG/39(37.14)
rs1048101	ADRA1A	GG/77(73.33)	GA/26(24.76)	AA/2(1.90)
rs776746	CYP3A5	CC/45(42.86)	CT/51(48.57)	TT/9(8.57)
rs7297610	YEATS4	CC/95(90.48)	CT/7(6.67)	TT/3(2.86)
rs4344	ACE	AA/47(44.76)	AG/41(39.05)	GG/17(16.19)
rs5522	NR3C2	TT/65(61.91)	TC/33(31.43)	CC/7(6.67)
rs4149056	SLCO1B1	TT/86(81.90)	TC/11(10.48)	CC/8(7.62)
rs5186	AGTR1	AA/88(83.81)	AC/11(10.48)	CC/6(5.71)
rs5443	GNB3	TT/32(30.48)	TC/57(54.29)	CC/16(15.24)

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表 4 两组各指标比较(x±s)

Table 4. Comparison of indicators between the two groups (x±s)

项目	时间(月)	试验组	对照组	F值			P值
项目	时间(月)	试验组	对照组	组别	时间	组别×时间	组别	时间	组别×时间
收缩压(mmHg)	0	150.20±11.86	151.08±11.68	1.999	240.972	18.957	0.160	< 0.001	< 0.001
	3	139.43±9.24^b	144.85±8.75^b	16.988			< 0.001
	6	133.67±7.85^b	139.93±8.29^b	28.513			< 0.001
舒张压(mmHg)	0	96.09±7.55	96.73±9.81	1.226	1 009.375	224.591	0.271	< 0.001	< 0.001
	3	93.84±8.17^b	96.02±9.49	14.998			< 0.001
	6	83.37±9.58^b	90.41±9.18^b	284.746			< 0.001
BMI(kg/m²)	0	24.96±5.74	25.06±4.28	0.001	0.802	0.019	0.976	0.450	0.981
	3	24.71±5.04	24.87±4.74	0.025			0.875
	6	24.43±4.40	24.39±4.45	0.018			0.895
FBG(mmol/L)	0	6.88±1.83	6.97±1.85	0.129	16.147	< 0.001	0.720	1.917	0.152
	3	6.50±1.54	6.66±1.89	0.489			0.486
	6	5.63±1.32^b	6.35±1.76^a	10.354			0.002
TC(mmol/L)	0	5.58±1.49	5.49±1.07	0.421	12.853	4.220	0.518	< 0.001	0.016
	3	5.27±1.32	5.40±1.16	0.446			0.506
	6	4.59±1.63^b	5.18±1.33	8.863			0.004
TG(mmol/L)	0	1.76±0.48	1.77±0.65	< 0.001	5.767	1.107	0.994	0.004	0.330
	3	1.63±0.53^a	1.73±0.58	1.638			0.203
	6	1.53±0.34^b	1..69±0.64	6.134			0.015
遵医服药行为得分	0	15.38±6.05	16.60±4.10	2.678	48.128	6.793	0.105	< 0.001	0.001
	3	18.16±3.77^b	17.04±4.43	8.108			0.005
	6	20.90±3.83^b	19.57±4.52^b	5.120			0.026
不良服药行为得分	0	26.12±6.67	25.09±6.20	1.073	58.387	5.775	0.303	< 0.001	0.004
	3	31.64±5.57^b	27.38±3.46^b	45.267			< 0.001
	6	32.09±5.34^b	30.70±4.29^b	4.369			0.039
日常生活管理行为得分	0	28.33±4.46	27.51±5.74	1.442	44.999	0.231	0.233	< 0.001	0.794
	3	32.74±8.23^b	31.54±8.85^b	0.888			0.348
	6	35.09±6.12^b	33.22±8.31^b	3.351			0.070
烟酒嗜好管理行为得分	0	6.39±2.56	6.83±1.92	1.817	8.854	2.877	0.181	< 0.001	0.059
	3	7.50±1.68^b	7.03±2.71	2.727			0.102
	6	7.35±2.12^b	7.63±1.71^b	1.275			0.262
依从性总分	0	76.21±9.50	76.12±9.91	< 0.001	153.463	6.589	0.989	< 0.001	0.002
	3	90.57±10.54^b	82.99±10.48^b	110.635			< 0.001
	6	95.43±8.96^b	91.12±10.46^b	76.668			< 0.001
注：与0个月时的值比较，^aP < 0.05, ^bP < 0.01。

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表 5 两组患者的不良反应率[n(%)]

Table 5. Proportion of adverse reactions in the two groups[n(%)]

干预时间 (d)	试验组 (n=105)	对照组 (n=104)	χ²值	P值
0	25(23.8)	23(25.5)	0.085	0.870
15	10(9.5)	21(20.6)	4.708	0.033
30	4(3.8)	18(17.6)	10.108	0.001
60	4(3.8)	19(15.7)	11.154	0.001

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