福建省畲族代谢综合征患者ATP2B1基因多态性与高血压遗传易感性的相关性研究

发布时间：2018-11-14 10:37

【摘要】：研究目的:代谢综合征和原发性高血压都是由多种基因、多种环境因素长期交互协同作用导致的慢性非传染性疾病。代谢综合征合并高血压患者的心血管风险显著增加。畲族人群是东南沿海主要的少数民族之一,目前尚缺乏畲族的相关研究。因此,本研究选择畲族人群代谢综合征患者,旨在研究高血压危险基因ATP2B1的rs2681472位点的多态性与高血压病的相关性,分析胎儿期饥荒暴露与血压水平的关系,以及基因-胎儿期饥荒暴露的交互作用与原发性高血压遗传易感性的关联。研究方法:采用病例对照设计方法,进行分层随机抽样,选取长期居住于宁德地区彼此无亲缘关系的20-80岁畲族人群代谢综合征患者共781人。其中男性215人,女性566人;高血压患者575人,无高血压者206人;胎儿期饥荒暴露者83人,未暴露者314人。采集人体测量学指标和临床生化指标,采集外周血用于DNA提取。采用Taqman探针法,在Real-time PCR(ABI 7500)仪进行基因分型。采用SPSS19.0软件进行数据分析。研究结果:(1)在畲族人群代谢综合征患者中,高血压组的ATP2B1基因rs2681472位点AG、GG基因型和G等位基因频率均高于非高血压组。危险等位基因G携带者患高血压的风险较A等位基因携带者高1.291倍(OR=1.291,95%CI:1.212-1.632,χ2=4.548,P=0.033)。不同基因型AA、AG、GG间,高血压的患病率依次增高。Logistic回归分析模型显示,调整了年龄、性别、BMI、身高、体重、腰围、TG、HDL-C、TC、LDL-C、FPG、OGTT-2h PG、吸烟和饮酒等因素,在加性效应模型下:AG基因型显著增加了高血压的患病风险(OR=1.923,CI:1.278-2.894,P=0.002),GG基因型增加了患高血压的风险,(OR=2.056,CI:1.028-4.110,P=0.041);GG基因型也与SBP正相关(OR=2.132,CI:1.103-4.119,P=0.041);在显性效应模型下,AG+GG显著增加高血压的患病风险,(OR=1.943,CI:1.308-2.886,P=0.001);也与SBP的正相关(OR=1.533,CI:1.056-2.226,P=0.025)。(2)采用非条件Logistic回归分析,校正年龄、性别、BMI等因素发现:胎儿期饥荒暴露组相比于未暴露组,其患高血压的风险显著增加(OR=2.109,CI:1.249-3.561,P=0.005),与SBP正相关(OR=2.420,CI:1.453-4.031,P=0.001)。(3)采用非条件Logistic回归分析,在调整年龄、性别、BMI、身高、体重、腰围、TG、HDLC、TC、LDL-C、FPG、OGTT-2h PG、吸烟和饮酒等因素,rs2681472位点的多态性和胎儿期饥荒暴露的交互作用对高血压的发病的无明显关联(P0.05)。代谢综合征患者在存在胎儿期饥荒暴露的情况下,携带危险等位基因G者较无危险等位基因者患高血压的风险增加2.187倍(OR=2.187,CI:1.157-4.135,P=0.015)。结论:代谢综合征患者中,ATP2B1基因rs2681472位点的基因多态性增加了高血压的易感性。携带危险等位基因G显著增加了高血压的患病风险,且与SBP正相关。胎儿期饥荒暴露显著增加了高血压患病风险,且与SBP正相关。胎儿期饥荒暴露为代谢综合征病人患高血压病的独立危险因素。ATP2B1的SNP位点rs2681472的多态性和胎儿期饥荒暴露的交互作用与高血压的遗传易感性无明显关联。在存在胎儿期饥荒暴露的情况下,携带危险等位基因G者较无危险等位基因者患高血压的风险增加。
[Abstract]:Objective: The metabolic syndrome and essential hypertension are chronic non-communicable diseases caused by long-term interaction of multiple genes and various environmental factors. The risk of cardiovascular risk in patients with metabolic syndrome complicated with hypertension is significantly increased. The ethnic group is one of the major ethnic minorities in the southeast coast, and there is no relevant research on the minority nationality at present. The aim of this study is to study the relationship between the polymorphism of the rs2681472 site of the hypertension risk gene, ATP2B1 and the hypertension, and to analyze the relationship between the exposure of the Famine and the blood pressure in the fetus. and the association of the interaction of gene-fetal-phase famine exposure with the genetic susceptibility of essential hypertension. Methods: A case-control design method was used for stratified random sampling, and a total of 781 patients with metabolic syndrome in the 20-80-year-old group with no genetic relationship with each other in the Ningde region were selected. Of these, there are 215 men, 566 women, 575 in high blood pressure, 206 without hypertension, 83 in the fetus and 314 in the unexposed. the human body measurement index and the clinical biochemical index are collected, and the peripheral blood is collected for DNA extraction. Genotyping was performed using the Taqman probe method in a Real-time PCR (ABI 7500) instrument. Data analysis was performed using the SPSS19.0 software. Results: (1) The ATP2B1 gene rs2681472, AG, GG genotype and G allele frequency of the hypertension group were higher than that of the non-hypertension group in the patients with metabolic syndrome in the family. The risk of high blood pressure was 1.291 (OR = 1.291, 95% CI: 1.212-1.632, Sup2 = 4.548, P = 0.033). The prevalence of hypertension among different genotypes of AA, AG and GG was increased. The Logistic regression analysis model showed that the age, sex, BMI, height, body weight, waist circumference, TG, HDL-C, TC, LDL-C, FPG, OGTT-2h PG, smoking and drinking were adjusted. Under the additive effect model, the AG genotype significantly increased the risk of hypertension (OR = 1.923, CI: 1.278-2.894, P = 0.002). GG genotype increased the risk of hypertension (OR = 2.056, CI: 1,028-4.110, P = 0.041); GG genotype was also positively related to SBP (OR = 2.132, CI: 1.103-4.119, P = 0.041); in the dominant effect model, AG + GG significantly increased the risk of hypertension, (OR = 1.943, CI: 1.308-2.886, P = 0.001); and was also positively related to the SBP (OR = 1.533, CI: 1.056-2.226,P=0.025). (2) By non-conditional logistic regression analysis, the factors such as age, sex, BMI and other factors were found: the risk of hypertension was significantly increased (OR = 2.109, CI: 1.249-3.561, P = 0.005) compared with that of unexposed group (OR = 2.420, CI: 1.453-4.31, P = 0.001). (3) The factors such as age, sex, BMI, height, body weight, waist circumference, TG, HDLC, TC, LDL-C, FPG, OGTT-2h PG, smoking and drinking were analyzed by non-conditional logistic regression analysis. The association between the polymorphism of rs2681472 and the exposure of famines in the fetus was not associated with the incidence of hypertension (P0.05). The risk of hypertension was increased by 2.187-fold (OR = 2.187, CI: 1.157-4.135, P = 0.015) in patients with metabolic syndrome in the presence of famines in the fetus. Conclusion: In the patients with metabolic syndrome, the genetic polymorphism of the ATP2B1 gene rs2681472 has increased the susceptibility of hypertension. Carrying the risk allele G significantly increases the risk of hypertension and is associated with the SBP. Famine exposure in the fetus significantly increased the risk of hypertension and was positively associated with the SBP. Famine exposure in the fetus is an independent risk factor for hypertension in patients with metabolic syndrome. The polymorphism of the SNP locus rs2681472 of ATP2B1 and the interaction of the exposure of the famines in the fetus were not significantly associated with the genetic susceptibility of hypertension. In the presence of an exposure to the famines in the fetus, the risk of high blood pressure is increased with the risk allele G being less likely to have a risk allele.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R589;R544.1

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