本文選題：MTHFR酶 + 多態(tài)性��； 參考：《青海大學(xué)》2017年碩士論文

【摘要】：目的初步了解青海地區(qū)藏族原發(fā)性高血壓(Essential hypertension,EH)人群,血漿同型半胱氨酸(Homocysteine,Hcy)的濃度,明確Hcy的濃度差異是否與調(diào)節(jié)其代謝或運(yùn)轉(zhuǎn)的酶基因多態(tài)性有關(guān),并探討Hcy與亞甲基四氫葉酸還原酶(methylenetetrahydrofolate reductase,MTHFR)A1298C位點(diǎn)變異同青海地區(qū)藏族EH是否有因果關(guān)聯(lián),從而極大程度地為青海地區(qū)藏族EH的提前預(yù)警,針對(duì)性治療增加獨(dú)特的參考價(jià)值。方法收集2015.8-2016.12青海省人民醫(yī)院心血管內(nèi)科就診治療的藏族EH人群60例,男34例,女26例,平均年齡58.97±13.38歲,非EH組為2015.8-2016.12(相同時(shí)期)本院門診體檢的無高血壓青海藏族人群,年齡和性別與EH組分別相互對(duì)應(yīng),總計(jì)75例,男40例,女35例,平均年齡55.58±11.22歲。采集經(jīng)過EDTA抗凝的空腹靜脈血,盡量保證在一小時(shí)內(nèi)離心完畢,精密量取8μl血漿用Hcy測定儀速率法精密地定量測出Hcy水平;白細(xì)胞層嚴(yán)格遵從QIAGEN公司供給的Gentra Puregene Handbook操作獲得純化DNA,使用聚合酶鏈限制性內(nèi)切酶片段長度多態(tài)性(PCR-RFLP)進(jìn)行目的片段擴(kuò)增,檢測MTHFRA1298C的rs1801131位點(diǎn)變異情況,比較MTHFRA1298C基因型與等位基因在青海藏族EH組與非EH組的分布情況,及其相對(duì)應(yīng)的Hcy水平特征,分析它們同EH是否存在因果關(guān)聯(lián)。結(jié)果(1)青海藏族高血壓組血漿Hcy水平為19.02±8.31μmol/L,高于對(duì)照組15.65±5.76μmol/l,且差異具有顯著性(P0.05)。青海藏族MTHFRA1298C各基因型AA的Hcy水平為17.42±6.33μmol/l、AC為19.47±8.24μmol/l、CC的16.45±7.30μmol/l,三者的濃度用One-Way ANOVA analysis進(jìn)行對(duì)比,三者相互間差異都無顯著性(P=0.233)。通過多因子的二元Logistic回歸在控制血脂、體重指數(shù)混雜因子后,并未發(fā)現(xiàn)Hcy能作為EH的孤立風(fēng)險(xiǎn)因子單獨(dú)使其風(fēng)險(xiǎn)升高(OR=1.567,95%CI:0.513-4.788,P0.05)。(2)EH組MTHFRA1298C基因AA、AC和CC頻率分別為56.67%、38.33%、5.00%,A、C頻率分別為75.83%、24.17%;對(duì)照組AA、AC和CC頻率分別為61.33%、30.67%、8.00%,A、C分別為76.67%、23.33%,MTHFRA1298C的rs1801131位點(diǎn)的分布通過卡方檢驗(yàn),得出在青海地區(qū)藏族人群的EH組與對(duì)照組均無顯著差別(P值均大于0.05)。高血壓組MTHFRA1298C基因AA、AC+CC頻率分別56.67%、43.33%,對(duì)照組AA、AC+CC頻率分別61.33%、38.67%,兩組AA、AC+CC分布無顯著差別(P=0.583)。結(jié)論(1)EH組的血漿Hcy濃度顯著高于非EH組,然而,Hcy并不是EH的風(fēng)險(xiǎn)因子。(2)青海藏族MTHFRA1298C位點(diǎn)變異并不影響血漿Hcy濃度發(fā)生變化。(3)MTHFRA1298C位點(diǎn)變異同青海藏族EH人群并沒有顯著的因果關(guān)聯(lián)。
[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 鹵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 鹵13.38 years. Age and sex corresponded to each other in EH group (75 cases, male 40, female 35, mean age 55.58 鹵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 鹵8.31 渭 mol / L, which was higher than that in the control group (15.65 鹵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 鹵6.33 渭 mol / L and 19.47 鹵8.24 渭 mol / L, 16.45 鹵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.
【學(xué)位授予單位】：青海大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R544.11

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