本文選題：非酒精性脂肪性肝病 + 維吾爾族�。� 參考：《新疆醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:探討新疆維吾爾族人群5,10-亞甲基四氫葉酸還原酶(MTHFR)及甲硫氨酸合成酶還原酶(MTRR)基因多態(tài)性與非酒精性脂肪肝(NAFLD)的相關(guān)性。方法:在新疆醫(yī)科大學(xué)第一附屬醫(yī)院病區(qū)收集325例NAFLD患者和新疆醫(yī)科大學(xué)健康管理中心體檢部收集325例健康體檢者共650例;均進(jìn)行問(wèn)卷調(diào)查、體格檢查和血液生化指標(biāo)等檢測(cè)。對(duì)MTHFR、MTRR基因多態(tài)性運(yùn)用多重高溫連接酶檢測(cè)反應(yīng)技術(shù)(i MLDR)進(jìn)行檢測(cè),比較等位基因及基因型在NAFLD組與對(duì)照組中的分布頻率及差異并于NAFLD的關(guān)聯(lián)性。結(jié)果:1)NAFLD組體重、WC、DBP、SBP、BMI、WHtR均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。2)NAFLD組AST、ALT、TC、TG、FPG、LDL-C、UA、Hb A1c水平高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。3)患有高血壓、糖尿病和冠心病者在NAFLD組與對(duì)照組均有統(tǒng)計(jì)學(xué)差異(P0.05);高血壓病家族史、糖尿病家族史、冠心病家族史和腫瘤家族史在兩組間有統(tǒng)計(jì)學(xué)差異(P0.05)。4)多因素的logistic回歸分析顯示,肥胖患者患NAFLD的風(fēng)險(xiǎn)增加了4.005倍(OR=4.005,95%CI=2.138-7.499);腹性肥胖患者患NAFLD的風(fēng)險(xiǎn)增加了6.396倍(OR=6.396,95%CI=2.394-17.085);高血糖患者患NAFLD的風(fēng)險(xiǎn)增加了8.045倍(OR=8.045,95%CI=1.889-34.258);高甘油三酯患者患NAFLD的風(fēng)險(xiǎn)增加了2.770倍(OR=2.770,95%CI=1.329-5.775);低-高密度脂蛋白血癥患者患NAFLD的風(fēng)險(xiǎn)增加了6.908倍(OR=6.908,95%CI=2.000-23.864);高-低密度脂蛋白血癥患者患NAFLD的風(fēng)險(xiǎn)增加了3.344倍(OR=3.344,95%CI=1.228-9.103);ALT異�；颊呋糔AFLD的風(fēng)險(xiǎn)增加了3.795倍(OR=3.795,95%CI=1.500-9.603)。5)MTHFR基因rs1801133多態(tài)性位點(diǎn)的GG、GA、AA基因型和G、A等位基因在NAFLD組與對(duì)照組中分布無(wú)統(tǒng)計(jì)學(xué)差異(χ2=1.776,P=0.411;χ2=1.520,P=0.218;P0.05)。在女性人群中,加性遺傳模型AA基因型的個(gè)體攜帶者患NAFLD的風(fēng)險(xiǎn)顯著升高,是NAFLD的危險(xiǎn)因素(GG、GA vs AA,OR=2.699,95%CI=1.243-5.859,P=0.010);在隱性遺傳模型中,AA基因型的個(gè)體攜帶者患NAFLD的風(fēng)險(xiǎn)顯著升高,是NAFLD明顯的危險(xiǎn)因素(GG+GA vs AA,OR=2.444,95%CI=1.158-5.158,P=0.016);在等位基因中,A等位基因個(gè)體攜帶者患NAFLD的風(fēng)險(xiǎn)顯著升高(G vs A,OR=1.473,95%CI=1.068-2.031,P=0.018),而男性人群在遺傳模型及等位基因與NAFLD無(wú)易感性(P0.05)。在NAFLD患者中(男+女),AA基因型攜帶者FPG水平顯著高于GG、GA(AAGGGA)基因型攜帶者;AA基因型攜帶者的AST水平顯著高于GG、GA(AAGAGG)基因型攜帶者。在男性NAFLD患者中,GG基因型攜帶者的DBP水平顯著高于GA、AA(GGGAAA)基因型攜帶者;AA基因型攜帶者的AST水平顯著高于GA、GG(AAGAGG)基因型攜帶者。在女性NAFLD患者中,AA基因型攜帶者的BMI、腰圍、DBP水平顯著高于GA、GG(AAGAGG)基因型攜帶者;AA基因型攜帶者的FPG水平顯著高于GG、GA(AAGGGA)基因型攜帶者,差異均具有統(tǒng)計(jì)學(xué)意義(P0.05),而其它臨床生化指標(biāo)在不同基因型之間均無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。6)MTHFR基因rs1801131多態(tài)性位點(diǎn)的TT、GT、GG基因型和T、G等位基因在NAFLD組與對(duì)照組中分布的差異無(wú)統(tǒng)計(jì)學(xué)意義(χ2=1.187,P=0.552;χ2=0.004,P=0.951;P0.05);MTHFR基因rs1801131多態(tài)性位點(diǎn)在遺傳模型中均與NAFLD無(wú)易感性(P0.05)。在NAFLD患者中(男+女),GG基因型攜帶者的TC水平顯著高于TT、GT(GGTTGT)基因型攜帶者;在男性NAFLD患者中,GG基因型攜帶者的TC水平顯著高于TT、GT(GGTTGT)基因型攜帶者;在女性NAFLD患者中,GG基因型攜帶者的LDL-C水平顯著高于TT、GT(GGTTGT)基因型攜帶者,差異均有統(tǒng)計(jì)學(xué)意義(P0.05),其它臨床生化指標(biāo)在不同基因型之間差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。7)MTRR基因rs1801394多態(tài)性位點(diǎn)的AA、GA、GG基因型和A、G等位基因在NAFLD組與對(duì)照組中分布的差異無(wú)統(tǒng)計(jì)學(xué)意義(χ2=1.179,P=0.555;χ2=0.911,P=0.340;P0.05);MTRR基因rs1801394位點(diǎn)在遺傳模型中均與NAFLD無(wú)易感性(P0.05);在NAFLD患者的生化指標(biāo)在不同基因型之間差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:1)在維吾爾族人群中BMI、WC、WHtR與NAFLD的發(fā)生有關(guān)。肥胖,高血糖,腹性肥胖,高甘油三脂血癥,低-高密度脂蛋白血癥、高-低密度脂蛋白血癥和ALT異常是NAFLD發(fā)生的危險(xiǎn)因素。2)MTHFR基因rs1801133多態(tài)性位點(diǎn)可能與新疆地區(qū)維吾爾族人群非酒精性脂肪肝的發(fā)生有關(guān)聯(lián)。尤其在女性人群中,攜帶A等位基因和突變純合子AA基因的個(gè)體發(fā)生非酒精性脂肪肝的風(fēng)險(xiǎn)顯著升高。MTHFR基因rs1801133多態(tài)性位點(diǎn)對(duì)FPG、AST、DBP、BMI、WC水平有影響。3)在維吾爾族人群中,MTHFR基因rs1801131多態(tài)性位點(diǎn)與NAFLD的發(fā)生無(wú)相關(guān)性。MTHFR基因rs1801131多態(tài)性位點(diǎn)對(duì)TC、LDL-C水平有影響。4)在維吾爾族人群中,MTRR基因rs1801394多態(tài)性位點(diǎn)與NAFLD無(wú)相關(guān)性。
[Abstract]:Objective: To investigate the association of 5,10- methylene four hydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphism with non-alcoholic fatty liver (NAFLD) in Xinjiang Uygur population. Methods: 325 cases of NAFLD patients and health management center of Xinjiang Medical University were collected at the First Affiliated Hospital of Xinjiang Medical University. A total of 325 healthy persons were collected in 650 cases. All of them were investigated by questionnaire, physical examination and blood biochemical indexes. MTHFR, MTRR gene polymorphism was detected by multiple high temperature ligase detection reaction (I MLDR), and the distribution frequency and difference of allele and genotype in NAFLD group and control group were compared and the relationship between NAFLD and allele was compared. Results: 1) the weight of NAFLD group, WC, DBP, SBP, BMI, WHtR were higher than those of the control group, and the difference was statistically significant (P0.05).2) NAFLD group AST, ALT, there was a higher level than the control group, the difference was statistically significant between the patients with high blood pressure, diabetes and coronary heart disease. Family history of disease, family history of diabetes, family history of coronary heart disease and family history of tumor were statistically different between the two groups (P0.05).4) multiple factors logistic regression analysis showed that the risk of NAFLD increased by 4.005 times (OR=4.005,95%CI=2.138-7.499) in obese patients, and the risk of NAFLD in abdominal obesity increased by 6.396 times (OR=6.396,95%CI=2.394-17.). 085); the risk of NAFLD increased by 8.045 times (OR=8.045,95%CI=1.889-34.258) in patients with hyperglycemia; the risk of NAFLD increased by 2.770 times (OR=2.770,95%CI=1.329-5.775) in patients with high triglycerides; the risk of NAFLD increased by 6.908 times (OR=6.908,95%CI=2.000-23.864) in patients with low high density lipoproteinemia; patients with high low density lipoproteinemia were affected by hyperglycemia. The risk of NAFLD increased by 3.344 times (OR=3.344,95%CI=1.228-9.103); the risk of NAFLD in patients with ALT abnormalities increased by 3.795 times (OR=3.795,95%CI=1.500-9.603).5) the GG of the MTHFR gene rs1801133 polymorphism sites, GA, AA genotype and G, and there was no statistical difference between the group and the group (chi square) =0.218; P0.05). In the female population, the risk factor of NAFLD is significantly higher in the individual carriers of the additive genetic model AA genotype, which is a risk factor for NAFLD (GG, GA vs AA, OR=2.699,95%CI=1.243-5.859, P=0.010). GA vs AA, OR=2.444,95%CI=1.158-5.158, P=0.016); in the allele, the risk of NAFLD is significantly higher in individual carriers of A allele (G vs A, OR=1.473,95%CI=1.068-2.031, P=0.018), while the male population is in the genetic model and allele. The GA (AAGGGA) genotype carrier was higher than GG, and the AST level of the AA genotype carriers was significantly higher than that of GG, GA (AAGAGG) genotype carriers. In male NAFLD patients, the DBP level of the GG genotype carriers was significantly higher than that of the GA and genotype carriers; the genotype carrier was significantly higher than that of the genotype carriers. In the patients with sex NAFLD, the BMI, waist circumference and DBP level of the AA genotype carriers were significantly higher than those of GA and GG (AAGAGG) genotype carriers, and the FPG levels of AA genotype carriers were significantly higher than those of GG, GA (AAGGGA) genotype carriers, but the clinical biochemical indexes were not statistically different among the different genotypes. 6) there was no significant difference in the distribution of TT, GT, GG genotypes and T, G alleles in the MTHFR gene rs1801131 polymorphism loci between the NAFLD group and the control group (x 2=1.187, P=0.552, Chi 2=0.004, P=0.951, etc.). The TC level of the type carrier was significantly higher than that of the TT, GT (GGTTGT) genotype carrier, and in the male NAFLD patients, the TC level of the GG genotype carriers was significantly higher than that of TT and GT (GGTTGT) genotype carriers; in female NAFLD patients, the level of the GG genotyped carriers was significantly higher than that of the genotype carriers. 05), there was no significant difference in other clinical biochemical indexes between different genotypes (P0.05).7) AA, GA, GG genotype and A, G allele and G alleles in the NAFLD group and the control group, and there was no statistical difference between the NAFLD group and the control group (x 2=1.179, P= 0.555; chi square). There was no susceptibility to NAFLD in the model (P0.05), and there was no significant difference between the biochemical indexes of NAFLD patients in different genotypes (P0.05). Conclusion: 1) in Uygur population, BMI, WC, WHtR are associated with NAFLD. Obesity, hyperglycemia, abdominal obesity, hyperglycerin, hyperglycemia, low high density lipoproteinemia, high low density lipoprotein, and high density lipoprotein The MTHFR gene rs1801133 polymorphic loci may be associated with the occurrence of non-alcoholic fatty liver in the Uygur population in Xinjiang. Especially in women, the risk of carrying non-alcoholic fatty liver with the A allele and the mutant homozygous AA gene in the female population is significantly higher in the female population,.2,.2.) the MTHFR gene rs1801133 polymorphism is associated with the risk of nonalcoholic fatty liver disease. The polymorphic loci of gene rs1801133 have influence on the level of FPG, AST, DBP, BMI, WC and.3) in Uygur population. There is no correlation between the rs1801131 polymorphism loci of MTHFR gene and the occurrence of NAFLD. Sex.
【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575.5

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