高血压及冠心病与人类β_3肾上腺素能受体多态性的关系

Relationship of hypertension and coronary heart disease with human β_3 adrenergic receptor gene polymorphism

目的:探讨β3肾上腺素能受体基因单核苷酸多态性与高血压、冠心病的关系。资料来源:应用计算机检索Medline1989-01/2004-03与高血压、冠心病及β3肾上腺素能受体基因单核苷酸多态性相关的文章,检索词“β3a-drenergicreceptor,polymorphism,hypertension,coronaryheartdisease”,并限定语言种类为英文。同时计算机检索中国期刊全文数据库1994/01-2004/03与高血压、冠心病及β3肾上腺素能受体基因单核苷酸多态性相关的文章,限定文章语言种类为中文,检索词“肾上腺素能受体,多态性,高血压,冠心病”。资料选择:对资料进行初审,选择包括和处理组和对照组的文献,筛除明显不符合研究目的文献,对剩余的文献开始查找全文。纳入标准为:①随机对照研究。②实验或临床研究包含平行对照组。排除重复性研究和综述类文章。资料提炼:共收集到27篇关于β3肾上腺素能受体多态性与高血压、冠心病的文章,17个实验研究符合纳入标准。排除的10篇为重复研究。资料综合:①β3的多态性与高血压相关,也与一些其他高血压发展的独立危险因子有关,如高血脂、肥胖、尿酸、瘦素浓度。因此,关于Arg64与高血压冠心病的相关性,还是不能区分是直接起于Arg64,还是继发于代谢相关的危险因子。②冠心病的发生是多因素、多基因作用的结果。不同的生活方式与环境因素都可能对β3受体基因Trp64Arg突变的作用产生增强或削弱的作用,因而不同地区的研究表现出不同的结果,也即是基因Trp64Arg突变对冠心病发生的影响可能存在人种与地区的差别。而作为冠心病危险因素之一的体质量指数与Trp64Arg基因多态性也存在相关,与脂代谢紊乱、胰岛素抵抗,以及瘦素水平增高有着密切的关系。所以,β3受体基因Trp64Arg突变可能在冠心病发病中有一定作用,但不是决定因素,也不是冠心病的主要预测因子。其对冠心病发生的影响可能是通过影响冠心病发生的潜在危险因素如体质量指数发挥作用。结论:冠心病和高血压是多种危险因素、多基因遗传的复杂病。高血压、冠心病与β3受体基因多态性的研究中关系怎样还是不明确。虽然β3受体基因Trp64Arg突变在高血压病和冠心病的遗传因素中不起主要作用,现在看来β3的多态性不太可能是疾病(如高血压和冠心病)的诱发基因,但他可能促使代谢疾病的早期发生,也许是一个重要的疾病危险因子,影响、调节疾病的进程。

OBJECTIVE： To study the association of the single nucleotide polymorphism in β3 adrenergic receptor gene with hypertension and coronary heart disease. DATA SOURCES： An online search of Medline database was undertaken to identify the articles about hypertension, coronary heart disease and single nucleotide polymorphism in β3 adrenergic receptor gene published in English between January 1989 and March 2004 by using the keywords of ＂β3 adrenergic receptor, polymorphism, hypertension, coronary heart disease＂; Meanwhile, Chinese articles about hypertension, coronary heart disease and β3-adrenoeptor gene single nucleotide polymorphism published from January 1994 and March 2004 were searched with computer in Chinese journals full-text database with the keywords of ＂adrenergic receptor, polymorphism, hypertension, coronary heart disease＂. STUDY SELECTION： After the preliminary searoh of the data, articles including treatment group and control group were selected, and the obvious irrelated studies were screened, and the full-texts of the rest articles were looked up. Inclusion criteria： ① randomized control study; ② experimental or clinical study containing parallel control group. The repetitive studies and reviews were excluded. DATA EXTRACTION： A total of 27 articles about β3 adrenergic receptor gene polymorphism, hypertension and coronary heart disease were collected, and 17 met the inclusion criteria, the 10 excluded ones were repetitive studies. DATA SYNTHESIS： ①The polymorphism of β3 was correlated with hypertension, also with other independent risk factors of the development of hypertension, such as hyperlipemia, obesity, uric acid and leptin concentration. So correlation between Arg64 and hypertension could not distinguish whether hypertension was originated from Arg64 or secondary from metabolism related risk factors. ② The occurrence of coronary heart disease was resulted from the actions of various factors and genes. Both different life style and environmental factors may enhance or reduce the β3 receptor gene Trp64Arg mutation, so studies of different areas showed different outcomes, that was to say the influence of Trp66Arg mutation on the occurrence of coronary heart disease may have the differences of race and area. As one of the risk factors of coronary heart disease, body mass index was associated with the Trp64Arg gene polymorphism, also had close correlation with lipid metabolic disorder, insulin resistance and increase of leptin level. So the β3 receptor gene Trp64Arg mutation might play a certain role in the attack of coronary heart disease, but it was not the decisive factor, also not the main predictor of coronary heart disease, its influence on the occurrence of coronary heart disease may action through affecting the potential risk factors of coronary, heart disease, such as body mass index. CONCLUSION： Corgnary heart disease and hypertension are the complex diseases of various risk factors and genetic heredity. The associations of β3 adrenergic receptor gene polymorphism with hypertension and coronary heart disease are still not clear. Although the β3 receptor gene Trp64Arg mutation does not play a main role in the genetic factors of hypertension and coronary heart disease, and the polymorphism of β3 is not possible the evoked gene of hypertension and coronary heart disease, it may accelerate the early occurrence of metabolic disease, may be an important risk factor of the diseases, and affects and adjusts the progress of the diseases.