β1-肾上腺素受体、血管紧张素Ⅱ-1型受体基因多态性与高寒地区高血压的关系研究

doi:10.12114/j.issn.1007-9572.2020.00.237

摘要/Abstract

摘要： 背景　高血压是最常见的慢性心血管病，也是全球疾病负担的主要原因，我国高血压发病率存在着地域差异，其中高寒地区高血压患者明显多于非高寒地区，这主要由生活环境和遗传因素决定，本文将从遗传学的角度对高血压的发病进行研究。目的　探究β1-肾上腺素受体（ADRB1）、血管紧张素Ⅱ-1型受体（AGTR1）基因多态性与高寒地区高血压的关系。方法　选取2014年8月—2017年2月于佳木斯大学附属第一医院高血压和心内科门诊就诊及住院的符合研究标准的高血压患者1 084例，其中546例进行ADRB1基因检测（记为高寒地区1组），702例进行AGTR1基因检测（记为高寒地区2组）。选取同期于本院进行体检的健康且未服用任何药物的志愿者169例（记为对照组受试者）。采用荧光染色原位杂交法检测所有受试者ADRB1、AGTR1基因型。比较高寒地区1组与对照组受试者ADRB1基因型、等位基因频率，高寒地区2组与对照组受试者AGTR1基因型、等位基因频率；并分析高寒地区高血压患者与非高寒（北京、湖南、福建）地区高血压患者及高寒地区健康人群与非高寒（北京、湖南、福建）地区高血压患者ADRB1、AGTR1基因型、等位基因频率。结果　高寒地区1组与对照组受试者ADRB1基因型比较，差异无统计学意义（P>0.05）；高寒地区1组与对照组受试者ADRB1等位基因频率比较，差异有统计学意义（P<0.05）。高寒地区2组与对照组受试者AGTR1基因型、等位基因频率比较，差异无统计学意义（P>0.05）。高寒地区1组高血压患者与北京地区、湖南地区、福建地区高血压患者ADRB1基因型、等位基因频率比较，差异无统计学意义（P>0.05）。高寒地区2组高血压患者与北京地区高血压患者AGTR1基因型、等位基因频率比较，差异无统计学意义（P>0.05）；高寒地区2组高血压患者与湖南地区、福建地区高血压患者AGTR1基因型、等位基因频率比较，差异有统计学意义（P<0.05）。对照组受试者与北京地区高血压患者ADRB1基因型比较，差异有统计学意义（P<0.05）；对照组受试者与北京地区高血压患者ADRB1等位基因频率比较，差异无统计学意义（P>0.05）；对照组受试者与湖南、福建地区高血压患者ADRB1基因型、等位基因频率比较，差异无统计学意义（P>0.05）。对照组受试者与北京地区高血压患者AGTR1基因型、等位基因频率比较，差异无统计学意义（P>0.05）；对照组受试者与湖南、福建地区高血压患者AGTR1基因型、等位基因频率比较，差异有统计学意义（P<0.05）。结论　ADRB1基因C等位基因与高寒地区高血压发病相关，暂未发现AGTR1基因多态性与高寒地区高血压发病相关。

关键词: 高血压；&beta, 1-肾上腺素受体；血管紧张素Ⅱ-1型受体；等位基因；高原病

Abstract: Background　Hypertension is the most common chronic cardiovascular disease and the leading cause of the global disease burden.There are regional differences in the incidence of hypertension in China，and more patients with hypertension are found in alpine areas than in non-alpine areas，which is mainly determined by living environment and genetic factors.This article will study the pathogenesis of hypertension from the perspective of genetics.Objective　To explore the association of gene polymorphisms in β1-adrenergic receptor（ADRB1） and angiotensionⅡ-1 receptor（AGTR1） with hypertension in alpine areas.Methods　A total of 1 084 patients with hypertension who met the research criteria seeking medical advice and hospitalization in Department of Hypertension and Department of Cardiology in the First Affiliated Hospital of Jiamusi University from August of 2014 to February of 2017 were selected.Among them，546 cases were tested for ADRB1 genotypes（recorded as Group 1），and 702 cases were tested for AGTR1 genotypes（recorded as Group 2）.And 169 healthy volunteers without taking any medicine were selected as the control group during the same period.The fluorescence in situ hybridization method was used to detect ADRB1 genotypes and AGTR1 genotypes.The ADRB1 genotypes and frequency of alleles between Group 1 and control group were compared and the AGTR1 genotypes and frequency of alleles between Group 2 and control group were compared.The ADRB1 genotypes and allele frequency，and AGTR1 genotypes and allele frequency between patients with hypertension in alpine areas and non-alpine areas（Beijing，Hunan，and Fujian），and healthy people in alpine areas and patients with hypertension in non-alpine areas（Beijing，Hunan，and Fujian） were compared.Results　There was no significant difference in the ADRB1 genotypes between Group 1 and control group（P>0.05），while there was significant difference in the ADRB1 allele frequency between Group 1 and control group（P<0.05）.There was no significant difference in the AGTR1 genotypes and allele frequency between Group 2 and control group（P>0.05）.There was no significant difference in the ADRB1 genotypes and allele frequency between patients with hypertension in Group 1 and in Beijing，Hunan and Fujian（P>0.05）.There was no significant difference in the AGTR1 genotypes and allele frequency between patients with hypertension in Group 2 and in Beijing（P>0.05），while there was significant difference in the AGTR1 genotypes and allele frequency between patients with hypertension in Group 2 and in Hunan and Fujian（P<0.05）.There was significant difference in the ADRB1 genotypes between volunteers in control group and patients with hypertension in Beijing（P<0.05），while there was no significant difference in the ADRB1 allele frequency between volunteers in control group and patients with hypertension in Beijing（P>0.05）.There was no significant difference in the ADRB1 genotypes and allele frequency between volunteers in control group and patients with hypertension in Hunan and Fujian（P>0.05）.There was no significant difference in the AGTR1 genotypes and allele frequency between volunteers in control group and patients with hypertension in Beijing（P>0.05）.There was significant difference in the AGTR1 genotypes and allele frequency between volunteers in control group and patients with hypertension in Hunan and Fujian（P<0.05）.Conclusion　The C allele in ADRB1 gene is associated with the onset of hypertension in alpine areas，and there is no association between the AGTR1 gene polymorphisms and the incidence of hypertension in alpine areas.

Key words: Hypertension；&beta, 1-adrenergic receptor；Angiotension Ⅱ-1 receptor；Alleles；Altitude sickness

王晶,董天崴,王爽,等. β1-肾上腺素受体、血管紧张素Ⅱ-1型受体基因多态性与高寒地区高血压的关系研究[J]. 中国全科医学, 2020, 23(30): 3823-3828. DOI: 10.12114/j.issn.1007-9572.2020.00.237.
WANG Jing,DONG Tianwei,WANG Shuang, et al. Association of Gene Polymorphisms in β1-adrenergic Receptor and Angiotension Ⅱ-1 Receptor with Hypertension in Alpine Areas　[J]. Chinese General Practice, 2020, 23(30): 3823-3828. DOI: 10.12114/j.issn.1007-9572.2020.00.237.

参考文献

［1］郑冬银.高血压个体化用药基因检测［J］．海峡药学，2018，30（8）：252-254．DOI：10.3969/j.issn.1006-3765.2018.08.141.
［2］封锐，王林，王罗莎.气象对心血管病影响的研究现状［J］．天津医药，2013，41（3）：282-284．DOI：10.3969/j.issn.0253-9896.2013.03.032.
［3］中国高血压防治指南修订委员会.中国高血压防治指南2010［J］.中华心血管病杂志，2011，39（7）：579-616.DOI：10.3760/cma.j.issn.0253-3758.2011.07.002.
［4］徐慧.原发性高血压病中医证型与高血压药物基因多态性的相关性研究［D］．北京：北京中医药大学，2018.
［5］刘洁，刘昭前，刘英姿.β1肾上腺素受体与CYP2D6基因多态性对美托洛尔抗高血压治疗的药代动力学和药效学影响［J］．中国临床药理学与治疗学，2007，12（10）：1130-1137．DOI：10.3969/j.issn.1009-2501.2007.10.006.
LIU J，LIU Z Q，LIU Y Z，et al．Effects of β1-adrenergic receptor and CYP2D6 genetic polymorphism on metoprolol pharmacokinetics and pharmacodynamics in antihypertension therapy［J］．Chinese Journal of Clinical Pharmacology and Therapeutics，2007，12（10）：1130-1137．DOI：10.3969/j.issn.1009-2501.2007.10.006.
［6］钟萍.β-AR基因多态性与EH的关联性及其与职业精神应激交互作用在EH高发人群中的致病作用［D］．福州：福建医科大学，2009.
ZHONG P.B-adrenergic receptor polymorphisms，occupational mental stress and their interaction involved in the pathogenesis of EH in the high risk population［D］．Fuzhou：Fujian Medical University，2009.
［7］ARNOLD A S，TANG Y L，QIAN K P，et al．Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia［J］．J Hypertens，2007，25（1）：197-205．DOI：10.1097/01.hjh.0000254374.73241.ab.
［8］LIU J，LIU Z Q，TAN Z R，et al．Gly389Arg polymorphism of beta1-adrenergic receptor is associated with the cardiovascular response to metoprolol［J］．Clin Pharmacol Ther，2003，74（4）：372-379．DOI：10.1016/S0009-9236（03）00224-8.
［9］PENG Y X，XUE H，LUO L M，et al．Polymorphisms of the beta1-adrenergic receptor gene are associated with essential hypertension in Chinese［J］．Clin Chem Lab Med，2009，47（10）：1227-1231．DOI：10.1515/CCLM.2009.276.
［10］李俊萍，郭晓华，郑玉云，等．β1肾上腺素能受体Gly389Arg多态性与原发性高血压的关系［J］．国际心血管病杂志，2006，33（4）：275-277.
［11］李强，杨新春，张麟.β1-肾上腺素能受体基因多态性与原发性高血压易感性［J］．中华心血管病杂志，2004，32（z1）：445．DOI：10.3760/j：issn：0253-3758.2004.z1.385.
［12］牛永红，谢正祥，殷跃辉.β肾上腺素能受体基因多态性与原发性高血压的关系［J］．中国组织工程研究与临床康复，2007，11（12）：2243-2246．DOI：10.3321/j.issn：1673-8225.2007.12.031.
NIU Y H，XIE Z X，YIN Y H.Beta-adrenoceptor gene polymorphism and essential hypertension［J］．Journal of Clinical Rehabilitative Tissue Engineering Research，2007，11（12）：2243-2246．DOI：10.3321/j.issn：1673-8225.2007.12.031.
［13］WANG H，LIU J L，LIU K，et al．Β1-adrenoceptor gene Arg389Gly polymorphism and essential hypertension risk in general population：a meta-analysis［J］．Mol Biol Rep，2013，40（6）：4055-4063．DOI：10.1007/s11033-012-2483-1.
［14］梁宇，赵彦艳，刘洪，等．β肾上腺素能受体基因家族在中国东北高血压病高发人群中的基因型分析［J］．中华医学遗传学杂志，2004，21（2）：124-127．DOI：10.3760/j.issn：1003-9406.2004.02.007.
LIANG Y，ZHAO Y Y，LIU H，et al．The genotype analysis of β adrenergic receptor gene family in high risk population of hypertension in northeast China［J］．Chinese Journal of Medical Genetics，2004，21（2）：124-127．DOI：10.3760/j.issn：1003-9406.2004.02.007.
［15］余惠珍，白玉茹，陈慧.AT1R基因和ACE基因多态性与高血压病的相关性分析［J］．高血压杂志，1999，7（4）：319．DOI：10.3969/j.issn.1673-7245.1999.04.014.
［16］孟超，陆惠华，方宁远，等．老年原发性高血压患者AT1-R基因A1166C多态性及降压药物对其的影响［J］．高血压杂志，2002，10（4）：347-351．DOI：10.3969/j.issn.1673-7245.2002.04.014.
MENG C，LU H H，FANG N Y，et al．The A1166C polymorphism of the Angiotensin Ⅱ type Ⅰ receptor gene and the response to antihypertensive agents in the elderly［J］．Chinese Journal of Hypertension，2002，10（4）：347-351．DOI：10.3969/j.issn.1673-7245.2002.04.014.
［17］KOOFFREH M E，ANUMUDU C I，DUKE R，et al．Angiotensin Ⅱ type 1 receptor A1166C gene polymorphism and essential hypertension in Calabar and Uyo cities，Nigeria［J］．Indian J Hum Genet，2013，19（2）：213-218．DOI：10.4103/0971-6866.116120.
［18］李涛，李南方，周玲，等．新疆哈萨克族人群中血管紧张素Ⅱ-1型受体基因多态性与原发性高血压的相关性研究［J］．临床心血管病杂志，2008，24（8）：606-608．DOI：10.3969/j.issn.1001-1439.2008.08.018.
LI T，LI N F，ZHOU L，et al．Study for relationship between the angiotensin Ⅱ type 1 receptor gene polymorphism and essential hypertension in Kazakans of Xinjiang［J］．Journal of Clinical Cardiology，2008，24（8）：606-608．DOI：10.3969/j.issn.1001-1439.2008.08.018.
［19］STANKOVIC A，ZIVKOVIC M，GLISIC S，et al．Angiotensin Ⅱ type 1 receptor gene polymorphism and essential hypertension in Serbian population［J］．Clin Chim Acta，2003，327（1/2）：181-185．DOI：10.1016/s0009-8981（02）00340-6.
［20］LIU D X，ZHANG Y Q，HU B，et al．Association of AT1R polymorphism with hypertension risk：an update meta-analysis based on 28，952 subjects［J］．J Renin Angiotensin Aldosterone Syst，2015，16（4）：898-909．DOI：10.1177/1470320315584096.
［21］何青芳，俞敏，王立新.血管紧张素Ⅱ-1型受体基因多态性与原发性高血压的相关性研究［J］．中华检验医学杂志，2006，29（9）：818-819.