青海藏族高血压患者Hcy及其代谢酶基因多态性研究

发布时间：2018-06-12 08:22

本文选题：MTHFR酶 + 多态性　；参考：《青海大学》2017年硕士论文

【摘要】：目的初步了解青海地区藏族原发性高血压(Essential hypertension,EH)人群,血浆同型半胱氨酸(Homocysteine,Hcy)的浓度,明确Hcy的浓度差异是否与调节其代谢或运转的酶基因多态性有关,并探讨Hcy与亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)A1298C位点变异同青海地区藏族EH是否有因果关联,从而极大程度地为青海地区藏族EH的提前预警,针对性治疗增加独特的参考价值。方法收集2015.8-2016.12青海省人民医院心血管内科就诊治疗的藏族EH人群60例,男34例,女26例,平均年龄58.97±13.38岁,非EH组为2015.8-2016.12(相同时期)本院门诊体检的无高血压青海藏族人群,年龄和性别与EH组分别相互对应,总计75例,男40例,女35例,平均年龄55.58±11.22岁。采集经过EDTA抗凝的空腹静脉血,尽量保证在一小时内离心完毕,精密量取8μl血浆用Hcy测定仪速率法精密地定量测出Hcy水平;白细胞层严格遵从QIAGEN公司供给的Gentra Puregene Handbook操作获得纯化DNA,使用聚合酶链限制性内切酶片段长度多态性(PCR-RFLP)进行目的片段扩增,检测MTHFRA1298C的rs1801131位点变异情况,比较MTHFRA1298C基因型与等位基因在青海藏族EH组与非EH组的分布情况,及其相对应的Hcy水平特征,分析它们同EH是否存在因果关联。结果(1)青海藏族高血压组血浆Hcy水平为19.02±8.31μmol/L,高于对照组15.65±5.76μmol/l,且差异具有显著性(P0.05)。青海藏族MTHFRA1298C各基因型AA的Hcy水平为17.42±6.33μmol/l、AC为19.47±8.24μmol/l、CC的16.45±7.30μmol/l,三者的浓度用One-Way ANOVA analysis进行对比,三者相互间差异都无显著性(P=0.233)。通过多因子的二元Logistic回归在控制血脂、体重指数混杂因子后,并未发现Hcy能作为EH的孤立风险因子单独使其风险升高(OR=1.567,95%CI:0.513-4.788,P0.05)。(2)EH组MTHFRA1298C基因AA、AC和CC频率分别为56.67%、38.33%、5.00%,A、C频率分别为75.83%、24.17%;对照组AA、AC和CC频率分别为61.33%、30.67%、8.00%,A、C分别为76.67%、23.33%,MTHFRA1298C的rs1801131位点的分布通过卡方检验,得出在青海地区藏族人群的EH组与对照组均无显著差别(P值均大于0.05)。高血压组MTHFRA1298C基因AA、AC+CC频率分别56.67%、43.33%,对照组AA、AC+CC频率分别61.33%、38.67%,两组AA、AC+CC分布无显著差别(P=0.583)。结论(1)EH组的血浆Hcy浓度显著高于非EH组,然而,Hcy并不是EH的风险因子。(2)青海藏族MTHFRA1298C位点变异并不影响血浆Hcy浓度发生变化。(3)MTHFRA1298C位点变异同青海藏族EH人群并没有显著的因果关联。
[Abstract]:Objective to investigate the plasma homocysteine (Hcy) concentration in the Tibetan essential hypertension (EH) population in Qinghai, and to determine whether the difference in Hcy concentration is related to the polymorphism of the enzyme gene that regulates its metabolism or operation. The relationship between the mutation of Hcy and methylenetetrahydrofolate reductase (MTHFRN A1298C) and Tibetan EH in Qinghai area was also discussed. The results indicated that Hcy and methylenetetrahydrofolate reductase (MTHFRN) A1298C mutation were causally related to the Tibetan EH in Qinghai area, thus providing a special reference value for Tibetan EH early warning and targeted therapy in Qinghai area. Methods A total of 60 Tibetan EH patients, 34 males and 26 females, with an average age of 58.97 卤13.38 years, were collected from the Department of Cardiovascular Medicine of Qinghai Provincial people's Hospital from May to December, 2015.The non-EH group was an outpatient check-up group of non-EH Tibetans with no hypertension in Qinghai province during the same period from May 8 to June 12, 2015.The average age was 58.97 卤13.38 years. Age and sex corresponded to each other in EH group (75 cases, male 40, female 35, mean age 55.58 卤11.22 years old). Fasting venous blood after EDTA anticoagulant was collected to ensure that 8 渭 l plasma was accurately measured by Hcy rate method in an hour after centrifugation. The leukocyte layer was obtained by strictly following the Gentra Puregene Handbook operation provided by QIAGEN. Polymerase chain restriction fragment length polymorphism (PCR-RFLP) was used to amplify the target fragment, and the variation of rs1801131 loci in MTHFRA1298C was detected. The distribution of MTHFRA1298C genotype and allele in Qinghai Tibetan EH group and non-EH group were compared, and the corresponding Hcy level characteristics were compared, and the causal relationship between MTHFRA1298C genotype and EH was analyzed. Results (1) the plasma Hcy level in Qinghai Tibetan hypertension group was 19.02 卤8.31 渭 mol / L, which was higher than that in the control group (15.65 卤5.76 渭 mol / L), and the difference was significant (P 0.05). The homocysteine level of AA in each genotype of Qinghai Tibetan MTHFRA1298C was 17.42 卤6.33 渭 mol / L and 19.47 卤8.24 渭 mol / L, 16.45 卤7.30 渭 mol / L, respectively. The concentrations of these three genotypes were compared with One-Way ANOVA analysis. There was no significant difference among the three genotypes (P0.233). After controlling for blood lipids and body mass index (BMI), multivariate logistic regression was used to analyze the relationship between blood lipids and body mass index. It was not found that Hcy can raise the risk of EH alone as an isolated risk factor for EH, and that the frequencies of AAC and CC of MTHFRA1298C gene in the EH group were 56.6767 ~ 38.335.005.005.005.005.005.00, respectively. The frequencies of AAC and CC in the control group were 61.3330.670.670.67and 8.00A respectively. The distribution of the rs1801131 site of MTHFRA1298C was 76.6767 ~ 23.333.339C, respectively. The results showed that there was no significant difference between the EH group and the control group in Qinghai Tibetan population (P > 0.05). The frequency of AAAC CC of MTHFRA1298C gene in hypertension group was 56.67 and that of control group was 61.338.67. there was no significant difference in the distribution of AAAC CC between the two groups. Conclusion the plasma Hcy concentration in the EH group is significantly higher than that in the non-EH group. However, Hcy is not a risk factor for EH.) the variation of MTHFRA1298C locus in Qinghai Tibetan does not affect the variation of plasma Hcy concentration. There is no significant causal correlation between the Hcy level variation and the Tibetan EH population in Qinghai.
【学位授予单位】：青海大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R544.11

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