中国农村地区高血压人群代谢综合征的流行病学调查及与心电图QTc、生长激素促泌素受体（GHSR）基因多态性的关联研究

【作者】 李卫菊；

【导师】 惠汝太；

【作者基本信息】 中国协和医科大学 ， 心血管内科， 2008， 博士

【摘要】 第一部分代谢综合征在农村高血压患者中的发病率及不同工作定义的比较目的比较最新3个不同代谢综合征定义,包括美国国家胆固醇教育计划ATPⅢ(NCEP)定义,美国心脏协会/心肺血液研究所(修订NCEP)定义,国际糖尿病联盟2005(IDF)定义,对高血压人群心血管疾病危险的识别。方法采用横断面研究,整群取样的方法,分析中国农村地区年龄40-75岁的高血压人群(5348人)应用不同诊断标准代谢综合征的患病率,并在高血压人群中,比较不同定义下的代谢综合征和冠心病、脑卒中的关系。结果分别采用NCEP、修订NCEP、IDF标准,在高血压人群,男性代谢综合征患病率分别为14%、32.9%、27.4%,女性代谢综合征患病率分别为35.6%、53.1%、50.2%;修订NCEP和IDF标准对代谢综合征诊断具有较高一致性,男性为94.4%,女性为97%:和NCEP、修订NCEP标准相比,IDF标准诊断的代谢综合征与冠心病的关联程度更高(校正后OR值女性为1.92[1.26-2.92]vs 1.85[1.13-3.03]、1.69[1.12-2.56];男性为1.64[1.29-2.10]vs 1.48[1.16-1.87]、1.60[1.25-2.05]),但是IDF标准诊断的代谢综合征和脑卒中弱相关或不相关。结论在高血压人群,修订NCEP及IDF定义较NCEP定义诊断的代谢综合征患病率高,且这两种定义有较高的诊断一致性;1DF定义的代谢综合征和冠心病关联程度更高。第二部分QTc间期和代谢综合征的关系背景QTc延长增加心血管发病率和死亡率,最近的研究表明:代谢综合征患者QTc延长,但是样本量较小,难以得出明确的结论。目的本研究在大样本人群中研究QTc和代谢综合征及其组分的关系,并对其可能的机制进行探讨。方法对象来源于河南信阳地区高血压调奄资料,共5815人(年龄20-80岁,男性1950人)入选。代谢综合征定义用修订的ATPⅢ标准。QTc用Bazett及Friderica公式计算,校正的JT间期(JTc)等于QTcB间期减去QRS间期。所有患者均进行心脏超声及血生化检查。结果代谢综合征人群比非代谢综合征人群有更长的QTc,在男性QTcB为439.84±50.89ms vs.430.90±48.15 ms,QTcF为427.96±51.93ms vs.420.23±40.24ms;在女性QTcB为456.37±56.43ms vs.445.17±48.09ms,QTcF为440.82±48.78 msvs.432.00±41.36ms,P值均小于0.001。同样,JTc在代谢综合征组也较非代谢综合征组延长,在男性为341.38±53.57ms vs.333.35±50.33ms,在女性为364.10±57.64ms vs.352.83±49.84ms。QTc和JTc随代谢异常组分增加而延长,趋势分析显示,在男性和女性,QTcB、QTcF、JTc和代谢综合征组分异常的数量显著性相关。在调整传统危险因素后,QTcB、QTcF、JTc和血清钾离子浓度负相关,和室间隔厚度正相关。结论代谢综合征是QTc延长的危险因素,QTc随着代谢综合征的发展逐渐延长。胰岛素抵抗与心肌肥厚和代谢综合征QTc的延长有关。第三部分Ghrelin受体单核苷酸多态性和代谢综合征的关联研究背景Ghrelin在能量代谢的调节方面具有重要作用,其受体是代谢综合征的候选基因。目的研究Ghrelin受体基因单核苷酸多态性与中国人群代谢综合征的关系。方法本研究采用病例对照的方法,病例和对照均来源于2005河南信阳地区高血压调查。以IDF2005代谢综合征诊断标准入选病例698(41-80岁)人,按性别年龄匹配的原则在同一人群选择对照762人。使用PCR和RFLP的方法对单核苷酸多态性位点(2个位于启动子区,1个位于内含子区)进行基因分型。卡方俭验比较不同基因型在组间的分布,Logistic回归分析基因型对代谢综合征及其组分的影响。结果rs2922126位点AA基因型频率在女性病例组显著高于对照组(25.1%vs18.1%,P＜0.05),AA基因型是女性代谢综合征的危险因素,校正年龄、吸烟及饮酒后OR值为1.41(95%CI,1.03-1.94),但在男性,病例组和对照组之间未见显著性差异。亚组分析表明,基因型AA是女性腰围增加及空腹血糖升高的危险因素,校正后OR值分别为1.75(95%CI,1.26-2.42),1.49(95%CI,1.07-2.06)。rs509030 AA基因型是女性高密度脂蛋白降低的危险因素OR值为1.37(95%CI,1.02-1.84)。P值均＜0.05。结论Ghrelin受体单核苷酸多态性和女性肥胖及糖脂代谢相关,提示在其女性代谢综合征的发病过程中有一定作用。更多还原

【Abstract】 Objectives To compare the prevalence of metabolic syndrome according to National Cholesterol Education Program ATPIII (NCEP), AHA/NHLBI revised-NCEP (the revised-NCEP) and International Diabetes Federation (IDF) definition and to investigate the association between metabolic syndrome and coronary heart disease and stroke in patients with hypertension.Methods In the Cross-section study, cluster sampling method was used. Three metabolic syndrome definitions were validated in 5348 hypertensive patients aged 40-75 years in rural areas in China.Results In subjects with hypertension, the prevalence of metabolic syndrome was 14%, 32.9%, and 27.4% in men; 35.6%, 53.1%, and 50.2% in women by NCEP, the revised-NCEP and IDF definition.The coincident rate percent was 94.4% in men, and 97.0% in women between revised NCEP and IDF definition. The IDF-defined metabolic syndrome was more strongly associated with coronary heart disease than the NCEP and revised NCEP defined metabolic syndrome (adjusted odds ratio: 1.92 [1.26-2.92] versus 1.85 [1.13-3.03] and 1.69 [1.12-2.56] in men; 1.64 [1.29-2.10] versus 1.48 [1.16-1.87] and 1.60 [1.25-2.05] in women), however, be weakly or not associated with stroke in the patients with hypertension.Conclusion In the patients with hypertension, the revised NCEP and IDF definition could identify more individuals with metabolic syndrome than did NCEP definition, and their accordance rate is very high. The IDF-defined metabolic syndrome seems to be more strongly associated with coronary heart disease than dose the NCEP and revised NCEP defined metabolic syndrome, however, be weakly or not associated with stroke. Background Prolongation of corrected QT interval (QTc) increases morbidity and mortality, the QTc has been found to be longer in persons with diabetes mellitus than in healthy controls.Purpose We hypothesized that metabolic syndrome might contribute risk to prolongation of QTc. The hypothesis was tested in a large population.Methods A total of 5815 individuals (men 1950, aged from 20 to 80 years) were enrolled. Metabolic syndrome was defined according to the revised NCEP-ATPIII. QTcB was calculated by using Bazett’s and QTcF by Fridericia equation, corrected JT interval (JTc) was derived by subtracting the QRS duration from the QTaB. All individuals had echocardiography and blood test.Results Individuals with metabolic syndrome had longer QTc and JTc than those without metabolic syndrome (439.84ms vs. 430.90 ms in men, 456.37ms vs. 445.17 ms in women respectively P<0.001 using Bazett formula). The more the number of abnormal metabolic parameters were, the longer QTc was. Strend analysis indicated that QTcB, QTcF and JTc were significantly correlated to the number of abnormal metabolic parameters both in men and in women. After adjusted for conventional risk factors, QTcB, QTcF and JTc remained to be negatively associated with serum potassium concentration and positively associated with ventricular septal thickness.Conclusion Metabolic syndrome is a risk factor for prolonged QTc which increases with the development of metabolic syndrome. Insulin resistence and myocardial hypertrophy may contribute to prolonged QTc. Background The ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene is an excellent candidate to study for metabolic syndrome.Aim In the present study, we investigated the association of single nucleotide polymorphisms in human ghrelin receptor gene with metabolic syndrome in Chinese.Methods A case control study, including 698 patients (aged 41 to 80 years) diagnosed with metabolic syndrome using IDF 2005 criteria and 762 age-and-sex matched controls, were conducted. Genotyping of three single nucleotide polymorphisms (two in promoter and one in intron) were performed by polymerase chain reaction and restriction fragment length polymorphism technique. Chi-Square test was used to compare the genotype distributions between two groups, and the logistic regression was used to analyze the contribution of gene variant to metabolic syndrome and its components.Results The frequency of the rs2922126 A/A genotype in promoter was higher in female metabolic syndrome group than in female control group (25.1% vs. 18.1%, P<0.05); and the rs2922126 A/A genotype was associated with female metabolic syndrome (adjusted OR, 95%CI: 1.41, 1.03-1.94). Further analysis in subgroups showed that it was associated with increased female waist circumference (1.75, 1.26-2.42) and higher female fast blood sugar (1.49, 1.07-2.06). Rs509030 A/A genotype was associated with lower female high density lipoprotein (1.37, 1.02-1.84).Conclusion single nucleotide polymorphisms in GHSR gene have some effects on obesity, glycometabolism and lipid metabolism in women, which suggests that they may be involved in progress of female metabolic syndrome.更多还原