本文選題：亞甲基四氫葉酸還原酶 + 基因多態(tài)性�。� 參考：《山東大學(xué)》2017年博士論文

【摘要】：引言嬰幼兒出生缺陷中,先天性心臟病是最常見類型,以死亡率高、花費高,給家庭、社會帶來沉重負(fù)擔(dān),盡管隨著醫(yī)療保險制度的完善,患兒家庭負(fù)擔(dān)在一定程度上減輕,但先天性心臟病所帶來的各種影響伴隨患兒一生。近些年來,隨著醫(yī)療技術(shù)的進(jìn)步,產(chǎn)前篩查的普及,先天性心臟病,尤其是復(fù)雜性先天性心臟病患兒的出生率明顯降低,但如何從病因上闡明先心病發(fā)病機(jī)制,從而根本上預(yù)防先天性心臟病的發(fā)生一直是研究難點。盡管目前對先心病的研究取得了較大進(jìn)步,且一刻未停,基因水平的研究也在不斷深入,但完全闡明先心病的發(fā)病機(jī)制及影響因素,依然任重道遠(yuǎn)�，F(xiàn)在比較被大多數(shù)研究者接受的理論認(rèn)為,先心病的發(fā)生是一綜合作用的結(jié)果,遺傳基因可能起主要作用,環(huán)境因素(輻射、污染、疾病等)是影響因素。查明與先心病發(fā)生有關(guān)的基因突變,探究其基因突變原因,進(jìn)而采取有針對性的預(yù)防措施,有助于降低先天性心臟病的發(fā)生。研究目的:探究沂蒙地區(qū)漢族先天性心臟病兒童亞甲基四氫葉酸還原酶(methylenetetrahydrofolate reductase,MTHFR)基因 C677T 的多態(tài)性分布,分析該地區(qū)漢族兒童MTHFR C677T基因與先天性心臟病發(fā)生的關(guān)聯(lián)性,了解該地區(qū)漢族兒童血漿同型半胱氨酸(Hcy)濃度水平,計算分析基因與血漿Hcy濃度水平的相關(guān)程度。探討MTHFR C677T基因在先心病發(fā)病機(jī)制中可能的作用,為先天性心臟病的病因及預(yù)防提供新線索。研究方法:選擇2014年10月至2016年6月,就診臨沂市人民醫(yī)院患有先天性心臟病的兒童110例作為病例組(CHD組),選擇同期就診該院查體的健康兒童110例作為對照組,兩組年齡均為1-5歲,平均3.2歲,性別、年齡均無統(tǒng)計學(xué)差異;取兩組兒童外周靜脈血進(jìn)行MTHFR C677T DNA提取和血漿同型半胱氨酸(Hcy)水平測定,并利用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性分析(PCR-RFLP)方法進(jìn)行基因分型,ELISA法測定血漿同型半胱氨酸水平。采用病例對照研究方法,分析基因C677T多態(tài)性與先天性心臟病發(fā)病及血漿同型半胱氨酸水平的相關(guān)性。結(jié)果:基因型CC、CT、TT,是MTHFRC677位點的三種基因型,等位基因T是突變基因;MTHFR基因C677T基因型CC、CT、TT型在CHD組和對照組的分布頻率分別為0.109、0.382、0.509 和 0.50、0.409、0.091,兩組間有顯著統(tǒng)計學(xué)差異χ2=59.796,P=0.000),CHD組含T基因型頻率明顯高于基因型CC頻率;等位基因C、T在CHD組與對照組頻率分別為0.30、0.70和0.705、0.295,兩組間具有顯著統(tǒng)計學(xué)差異(χ2=72.011,P=0.000),其中CHD組等位基因T基因頻率高于對照組等位基因T基因頻率。含突變等位基因T的基因型患先心病的風(fēng)險約是攜帶野生型等位基因C基因型的5.6倍(OR=5.564 95%CI3.697～8.373,P=0.000)。雜合子CT基因型患先心病的風(fēng)險高于野生型純合子基因型CC(OR=4.208,95%CI2.015～9.082,P=0.000);突變純合子TT基因型患先心病的風(fēng)險是野生型純合子CC基因型的25.667倍(95%CI 10.249～64.276,P=0.000),純合突變TT基因型對于先心病的致病風(fēng)險大。CHD組血漿同型半胱氨酸平均水平為(15.42±0.75umol/l)明顯高于對照組(7.48±0.37umol/l),MTHFR C677T基因型與血漿同型半胱氨酸水平具有相關(guān)性,Spearman相關(guān)系數(shù)為0.502。結(jié)論:沂蒙地區(qū)漢族先心病兒童和健康兒童中,MTHFR C677T基因具有多態(tài)性,其基因型頻率和等位基因頻率具有統(tǒng)計學(xué)差異(P0.05),先心病患兒中含等位基因T的基因型頻率及基因頻率較高;相關(guān)性分析示,突變等位基因T可能增加患先心病的風(fēng)險,而突變純合子TT基因型罹患患先心病的危險顯著增加;與對照組比較,血漿Hcy濃度在兒童先心病中明顯升高,并且MTHFR C677T基因與血漿Hcy濃度具有相關(guān)性,隨著含T基因型比例的升高,血漿同型半胱氨酸有升高趨勢。MTHFR基因C677T多態(tài)性可能是影響沂蒙地區(qū)漢族兒童罹患先天性心臟病的危險因素之一,其基因突變致心臟異常發(fā)育而引起先心病的機(jī)制復(fù)雜,推測血漿中高水平的同型半胱氨酸可能是影響因素之一。意義:該課題在設(shè)計上體現(xiàn)了"基因-疾病"的思路,研究群體的區(qū)域化,能夠在一定程度上減小周圍環(huán)境、飲食習(xí)慣等對研究結(jié)果的影響,此次研究系較早對沂蒙地區(qū)漢族兒童MTHFR C677T基因及血漿Hcy進(jìn)行分析,試圖探究該地區(qū)漢族兒童患先心病的相對危險基因及可能的作用機(jī)制;為從基因水平上研究先心病增加了新的認(rèn)識,為高危兒童予以早期干預(yù)措施提供理論依據(jù)。符合精準(zhǔn)醫(yī)療的發(fā)展趨勢,為基因篩查、治療提供線索。
[Abstract]:In the introduction of infant birth defects, congenital heart disease is the most common type, with high mortality, high cost and a heavy burden to the family and society. Although with the improvement of the medical insurance system, the family burden is alleviated to a certain extent, but the various effects of congenital heart disease are accompanied by the children's life. In recent years, with the medical treatment, with the medical treatment, with the medical treatment, with the medical treatment, with the medical treatment, with the medical treatment in recent years, along with the medical treatment The progress of the therapy, the popularization of prenatal screening, the birth rate of congenital heart disease, especially the children with complex congenital heart disease have been significantly reduced, but how to elucidate the pathogenesis of the congenital heart disease from the cause of the disease has been the difficulty in the study of congenital heart disease. The study of gene level is also going deep, but it is still a long way to go. It is now accepted by most researchers that the occurrence of congenital heart disease is the result of a comprehensive effect, the genetic gene may play a major role, environmental factors (radiation, pollution, disease). It is the influence factor. To find out the gene mutation related to the congenital heart disease, explore the cause of the gene mutation, and then take the pertinent preventive measures to help reduce the occurrence of congenital heart disease. The polymorphism distribution of eductase, MTHFR) gene C677T, analysis of the association between MTHFR C677T gene and congenital heart disease in Han children in this area, to understand the level of plasma homocysteine (Hcy) concentration in Han children in this area, to calculate the correlation between the analysis of gene and plasma Hcy concentration, and to explore the incidence of MTHFR C677T gene in the onset of congenital heart disease. The possible role of the mechanism to provide new clues for the cause and prevention of congenital heart disease. Methods: from October 2014 to June 2016, 110 children with congenital heart disease in Linyi people's hospital were selected as case group (group CHD), and 110 healthy children in the same period were selected as the control group, and the two groups were all aged. 1-5 years old, average 3.2 years, sex and age were not statistically different; two groups of peripheral venous blood were taken for MTHFR C677T DNA extraction and plasma homocysteine (Hcy) level, and polymerase chain reaction restriction fragment length polymorphism analysis (PCR-RFLP) method was used for genotyping and ELISA determination of plasma homocysteine The correlation between gene C677T polymorphism and congenital heart disease and plasma homocysteine levels was analyzed by case control study. Results: genotype CC, CT, TT, were three genotypes of MTHFRC677 loci and allele T was a mutant gene; MTHFR gene C677T genotype CC, CT, TT type were distributed frequency in CHD and control groups The rates were 0.109,0.382,0.509 and 0.50,0.409,0.091 respectively. There were significant statistical differences between the two groups. The frequency of T genotypes in the CHD group was significantly higher than the genotype CC frequency; the allele C and the frequency of T in the CHD group and the control group were 0.30,0.70 and 0.705,0.295. There were significant statistical differences between the two groups. The T gene frequency of the D allele was higher than the T allele frequency of the control group. The risk of congenital heart disease with the mutant allele T was about 5.6 times that of the C genotype of the wild type allele (OR=5.564 95%CI3.697 to 8.373, P=0.000). The risk of congenital heart disease in the heterozygote CT genotype was higher than that of the wild type homozygote genotype CC (OR=4.20) 8,95%CI2.015 ~ 9.082, P=0.000); the risk of congenital heart disease in the mutant homozygote TT genotype was 25.667 times that of the wild type homozygote CC genotype (95%CI 10.249 ~ 64.276, P=0.000). The average level of plasma homocysteine (15.42 + 0.75umol/l) in the large.CHD group of homozygous mutant TT genotypes was significantly higher than that of the control group (7.4 8 + 0.37umol/l), the genotype of MTHFR C677T was correlated with plasma homocysteine level, and the correlation coefficient of Spearman was 0.502. conclusion: the MTHFR C677T gene was polymorphic in the Han and healthy children of Yimeng Han and healthy children. The genotype frequency and allele frequency rate had statistical difference (P0.05), and the children with congenital heart disease contained the allele. The genotype frequency and gene frequency of the allele T were higher, and the correlation analysis showed that the mutation allele T might increase the risk of congenital heart disease, while the risk of congenital heart disease in the mutant homozygote TT genotype increased significantly. Compared with the control group, the plasma Hcy concentration was significantly higher in children with congenital heart disease, and the MTHFR C677T gene and plasma Hcy concentration were significantly higher. Degree of correlation, with the increase of T genotype ratio, the increase of plasma homocysteine trend.MTHFR gene C677T polymorphism may be one of the risk factors affecting congenital heart disease of Han children in Yimeng area. The mechanism of abnormal heart development caused by the mutation of the gene is complicated, and the high level of plasma is speculated. Homocysteine may be one of the influencing factors. Significance: the design embodies the idea of "gene disease", studies the regionalization of the population, and can reduce the influence of the surrounding environment and dietary habits to some extent. The study was earlier on the MTHFR C677T gene and plasma Hcy in the Han children in Yimeng area. In order to explore the relative risk genes and possible mechanisms of congenital heart disease in the Han children in this area, we try to provide a new understanding for the study of congenital heart disease from the gene level, and provide a theoretical basis for the early intervention measures for high risk children. It is in line with the trend of the development of precision medical treatment, and provides clues for gene screening and treatment.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R725.4

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 Reid G.J.;Webb G.D.;Barzel M.;黃浙勇;;先天性心臟病青少年和年輕患者自行估計的預(yù)期壽命[J];世界核心醫(yī)學(xué)期刊文摘(心臟病學(xué)分冊);2006年12期

2 閆躍中;武海波;張偉;張建偉;;長治市轄區(qū)11縣108864名小學(xué)生先天性心臟病調(diào)查[J];山西醫(yī)藥雜志;2011年03期

3 ;評估成人先天性心臟病病人的心理教育[J];國外醫(yī)學(xué).護(hù)理學(xué)分冊;1995年04期

4 陳魯玉;先天性心臟病患兒的術(shù)前護(hù)理[J];河南醫(yī)藥信息;2000年05期

5 何遠(yuǎn)峰;先天性心臟病患兒的觀察及護(hù)理體會[J];蛇志;2000年04期

6 劉愛梅,王德鳳,劉芹;微創(chuàng)治療先天性心臟病52例護(hù)理[J];中國煤炭工業(yè)醫(yī)學(xué)雜志;2000年10期

7 邵靜波;與先天性心臟病患兒手術(shù)年齡有關(guān)的因素[J];國外醫(yī)學(xué).心血管疾病分冊;2000年06期

8 胡寶璉;有了先天性心臟病的孩子怎么辦[J];醫(yī)藥世界;2000年12期

9 黃大鳴;嬰兒先天性心臟病的早期診斷[J];廣西醫(yī)學(xué);2001年03期

10 張萬青,李杰,何悅概,蘇庭寶,張光休,程可洛,陳捷,王志剛,黃一東,蔡小碧;兒童常見先天性心臟病術(shù)后超早期出院分析[J];中國航天工業(yè)醫(yī)藥;2001年04期

相關(guān)會議論文 前10條

1 林青枝;;慈溪市流動人口先天性心臟病病例對照研究[A];浙江省第十七屆農(nóng)村醫(yī)學(xué)暨鄉(xiāng)鎮(zhèn)衛(wèi)生院管理學(xué)術(shù)會議大會論文集[C];2009年

2 王浩;許聞橋;楊洪昌;段福建;張技革;周維新;葉贊凱;江勇;姚錚;;實時三維超聲心動圖對先天性心臟病的診斷價值[A];第九屆全國超聲醫(yī)學(xué)學(xué)術(shù)會議論文匯編[C];2006年

3 王惠軍;;先天性心臟病198例分析[A];第九屆全國超聲心動圖學(xué)術(shù)會議論文集[C];2007年

4 吳同果;肖強;閆承軍;景彩;;205例先天性心臟病介入治療體會[A];首屆中國先天性心臟病超聲診斷與介入治療暨手術(shù)演示學(xué)術(shù)會議論文集[C];2004年

5 陳昌珍;李鳳;;32例10公斤以下嬰幼兒先天性心臟病圍術(shù)期護(hù)理體會[A];全國內(nèi)科護(hù)理學(xué)術(shù)交流會議、全國心臟內(nèi)、外科護(hù)理學(xué)術(shù)交流會議、第9屆全國糖尿病護(hù)理學(xué)術(shù)交流會議、第9屆全國血液凈化護(hù)理學(xué)術(shù)交流會議論文匯編[C];2011年

6 周文浩;楊琳;詹國棟;王慧君;馬端;黃國英;;31例綜合征性先天性心臟病全基因組拷貝數(shù)變異分析[A];中華醫(yī)學(xué)會第十七次全國兒科學(xué)術(shù)大會論文匯編（上冊）[C];2012年

7 龔方戚;汪偉;;先天性心臟病介入治療進(jìn)展[A];2008年浙江省兒科學(xué)學(xué)術(shù)年會論文匯編[C];2008年

8 孟平;王曉敏;張艷麗;;先天性心臟病術(shù)后輸液的護(hù)理[A];2011年河南省靜脈輸液安全管理培訓(xùn)班及學(xué)術(shù)交流會議論文集[C];2011年

9 陳曉媛;蘇海礫;胡R，

本文編號：1969262