应用要点：试验观察了肝细胞生长因子的单核苷酸多态性分布与高血压发病的关系，而单核苷酸多态性作为一种分布广泛、遗传稳定的基因遗传标记，能充分地反映个体间的遗传差异。通过本课题的观察结果可能预测合肥地区汉族人群高血压的发病情况，及早提高预测青少年发生高血压的几率。

术语解析：单核苷酸多态性主要是指在基因组水平上由单个核苷酸的变异所引起的DNA序列多态性。频率大于1%。它是人类可遗传的变异中最常见的一种。单核苷酸多态性在人类基因组中广泛存在，平均每500~1 000个碱基对中就有1个，估计其总数可达300万个甚至更多。

偏倚或不足：①在试验的设计上，只是单纯分析了肝细胞生长因子的单核苷酸多态性与高血压发病间的可能关系，未能联合研究血肝细胞生长因子水平和单核苷酸多态性分布的关系，而进一步分析探讨血肝细胞生长因子水平具体受哪些单核苷酸多态性影响。②本试验采用的方法较为简单，仅观察了肝细胞生长因子的一个单核苷酸多态性位点，同时试验对象数目亦偏少。

摘要
目的:血管内皮细胞功能不全在高血压患者中普遍存在，肝细胞生长因子在内皮细胞功能不全中起重要作用，与高血压的流行、严重程度、靶器官受损等有关。探讨肝细胞生长因子基因C57488A的多态性在原发性高血压发病机制中的作用。
方法：①试验对象：选择2006-06/12在本院保健中心体检或本科室住院的原发性高血压患者共107例作为原发性高血压组，平均年龄（61±9）岁，其中有高血压家族史者共47例；所有对象均为合肥地区居住且无血缘关系的汉族人，患者对试验知情同意，试验经医院医学伦理委员会批准。病例收集按照中华医学会制订的高血压指南标准，收缩压≥140 mm Hg，或舒张压≥ 90 mm Hg (1 mm Hg=0.133 kPa)，或明确诊断为高血压而接受药物治疗达1年以上者。1个月内仅服用降压药。同时选择未曾接受高血压药物治疗的健康人共110名作为正常对照组，平均年龄（60±8）岁；纳入标准：收缩压< 140 mm Hg，舒张压< 90 mm Hg，并排除高血压家族史。所有受试对象均详细调查家族史，排除继发性高血压、糖尿病、冠心病、甲状腺疾病、严重的肝肾疾病及心肺功能不全等。②试验方法及评估：所有受试对象均测定血压、身高、体质量，计算出体质量指数，常规生化测定总胆固醇、三酰甘油、极低密度脂蛋白、空腹血糖等。采用单一等位基因特异性引物PCR技术测定两组肝细胞生长因子的基因型及肝细胞生长因子C57488A基因多态性分布、各基因型和等位基因频率分布。
结果：纳入原发性高血压患者107例和健康人110名，均进入结果分析。①原发性高血压组和正常对照组的年龄、性别、体质量指数、三酰甘油、总胆固醇、极低密度脂蛋白和空腹血糖差异均无显著性(P > 0.05)。②所有受试对象基因多态性分布符合Hardy-Weinberg平衡，具有群体代表性。原发性高血压组中有家族史者(47例)和无家族史者(60例)的CC、CA、AA基因型频率分别为0.809、0.170、0.021和0.733、0.233、0.033，C、A等位基因频率分别为0.894、0.106和0.850、0.150。正常对照组肝细胞生长因子基因C57488A 的CC、CA、AA基因型频率分别为0.527、0.355、0.060；C、A等位基因频率分别为0.705、0.295。③原发性高血压组中有家族史和无家族史者基因型CC和等位基因C频率均高于正常对照组(P < 0.01，P < 0.05)；有家族史者CC基因型频率和C等位基因频率均高于无家族史者，但差异无显著性 (P > 0.05)。
结论：合肥地区汉族人群原发性高血压的发生与肝细胞生长因子基因C57488A多态性有关，基因型CC和等位基因C可能是原发性高血压的易感因素。
关键词：肝细胞生长因子；原发性高血压；基因多态性

孟影，王邦宁.肝细胞生长因子基因C57488A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，2008，12(11):2043-2046 [www.zglckf.com/zglckf/ejournal/upfiles/08-11/11k-2043(ps).pdf]

Hepatocyte growth factor gene C57488A polymorphism and essential hypertension

Abstract

AIM：The impaired function of vascular endothelial cells occurs popularly in hypertensive patients. Hepatocyte growth factor (HGF) plays a crucial role on impaired function, and is related to prevalence, severity and target organ damages of hypertension. This study explored the relationship between HGF gene C57488A polymorphism and essential hypertension (EH).
METHODS: ①Between June and December in 2006, totally 107 EH patients with an average age of (61±9) years, in them 47 cases with family history of hypertension, were recruited in this study. Informed consents were obtained from the patients who were all the Han residents of Hefei area, and the experiment was approved by the hospital ethical committee. The hypertension criteria formulated by Chinese Medical Association included the systolic pressure ≥140 mm Hg or diastolic pressure ≥ 90 mm Hg (1 mm Hg=0.133 kPa), or having received drug therapy for hypertension over one year. The patients were administrated with hypotensive drugs with one month. Meanwhile 110 normotensives without family history of hypertension and drug therapy were served as controls, with an average age of (60±8) years. Inclusion criteria: systolic pressure < 140 mm Hg or diastolic pressure < 90 mm Hg (1 mm Hg=0.133 kPa). All the subjects were surveyed for family history, excluding secondary hypertension, diabetes, coronary heart disease, thyroid disease, severe liver and kidney disease, cardiorespiratory function insufficiency and so on.②Detection parameters included blood pressure, height, weight, body mass index, and total cholesterol, triacylglycerol, very low density lipoprotein, fasting blood glucose were detected biochemically. Single allele-special primer polymerase chain reaction technique was used to examine the polymorphism of HGF genetypes and distribution of allele frequency in two groups.
RESULTS: Both 107 EH patients and 110 healthy controls were involved in the result analysis.①There were no significant differences in age, sex, body mass index, total cholesterol, triacylglycerol, very low density lipoprotein and fasting blood glucose between the EH group and the controls (P > 0.05).②The distributions of HGF gene C57488A polymorphism were in agreement with Hardy-Weinberg equilibrium, indicating population representativeness. The frequencies of three genotypes CC, CA, AA were 0.809, 0.170, 0.021 and C, A alleles were 0.894, 0.106 in the EH group with family history respectively. Correspondingly, the frequencies were 0.733, 0.233, 0.033 and 0.850, 0.150 respectively in the EH patients without family history. Meanwhile, the frequencies were 0.527, 0.355, 0.060 and 0.705, 0.295 respectively in the controls.③The frequencies of genotype CC and allele C were both significant higher in EH with or without family history compared with the controls (P < 0.01, P < 0.05), but no significant difference was observed between the EH with family history and those without family history (P > 0.05).
CONCLUSION: HGF gene C57488A polymorphism is possibly associated with EH, and genotype CC and allele C may be the factors of genetic predisposition of EH in Han population of Hefei area.

Meng Y, Wang BN.Hepatocyte growth factor gene C57488A polymorphism and essential hypertension.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(11):2043-2046(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-11/11k-2043(ps).pdf]