新疆维吾尔族人群MTHFR、MTRR基因多态性与非酒精性脂肪肝的关系

发布时间：2018-06-15 11:39

本文选题：非酒精性脂肪性肝病 + 维吾尔族　；参考：《新疆医科大学》2017年硕士论文

【摘要】：目的:探讨新疆维吾尔族人群5,10-亚甲基四氢叶酸还原酶(MTHFR)及甲硫氨酸合成酶还原酶(MTRR)基因多态性与非酒精性脂肪肝(NAFLD)的相关性。方法:在新疆医科大学第一附属医院病区收集325例NAFLD患者和新疆医科大学健康管理中心体检部收集325例健康体检者共650例;均进行问卷调查、体格检查和血液生化指标等检测。对MTHFR、MTRR基因多态性运用多重高温连接酶检测反应技术(i MLDR)进行检测,比较等位基因及基因型在NAFLD组与对照组中的分布频率及差异并于NAFLD的关联性。结果:1)NAFLD组体重、WC、DBP、SBP、BMI、WHtR均高于对照组,差异有统计学意义(P0.05)。2)NAFLD组AST、ALT、TC、TG、FPG、LDL-C、UA、Hb A1c水平高于对照组,差异有统计学意义(P0.05)。3)患有高血压、糖尿病和冠心病者在NAFLD组与对照组均有统计学差异(P0.05);高血压病家族史、糖尿病家族史、冠心病家族史和肿瘤家族史在两组间有统计学差异(P0.05)。4)多因素的logistic回归分析显示,肥胖患者患NAFLD的风险增加了4.005倍(OR=4.005,95%CI=2.138-7.499);腹性肥胖患者患NAFLD的风险增加了6.396倍(OR=6.396,95%CI=2.394-17.085);高血糖患者患NAFLD的风险增加了8.045倍(OR=8.045,95%CI=1.889-34.258);高甘油三酯患者患NAFLD的风险增加了2.770倍(OR=2.770,95%CI=1.329-5.775);低-高密度脂蛋白血症患者患NAFLD的风险增加了6.908倍(OR=6.908,95%CI=2.000-23.864);高-低密度脂蛋白血症患者患NAFLD的风险增加了3.344倍(OR=3.344,95%CI=1.228-9.103);ALT异常患者患NAFLD的风险增加了3.795倍(OR=3.795,95%CI=1.500-9.603)。5)MTHFR基因rs1801133多态性位点的GG、GA、AA基因型和G、A等位基因在NAFLD组与对照组中分布无统计学差异(χ2=1.776,P=0.411;χ2=1.520,P=0.218;P0.05)。在女性人群中,加性遗传模型AA基因型的个体携带者患NAFLD的风险显著升高,是NAFLD的危险因素(GG、GA vs AA,OR=2.699,95%CI=1.243-5.859,P=0.010);在隐性遗传模型中,AA基因型的个体携带者患NAFLD的风险显著升高,是NAFLD明显的危险因素(GG+GA vs AA,OR=2.444,95%CI=1.158-5.158,P=0.016);在等位基因中,A等位基因个体携带者患NAFLD的风险显著升高(G vs A,OR=1.473,95%CI=1.068-2.031,P=0.018),而男性人群在遗传模型及等位基因与NAFLD无易感性(P0.05)。在NAFLD患者中(男+女),AA基因型携带者FPG水平显著高于GG、GA(AAGGGA)基因型携带者;AA基因型携带者的AST水平显著高于GG、GA(AAGAGG)基因型携带者。在男性NAFLD患者中,GG基因型携带者的DBP水平显著高于GA、AA(GGGAAA)基因型携带者;AA基因型携带者的AST水平显著高于GA、GG(AAGAGG)基因型携带者。在女性NAFLD患者中,AA基因型携带者的BMI、腰围、DBP水平显著高于GA、GG(AAGAGG)基因型携带者;AA基因型携带者的FPG水平显著高于GG、GA(AAGGGA)基因型携带者,差异均具有统计学意义(P0.05),而其它临床生化指标在不同基因型之间均无统计学差异(P0.05)。6)MTHFR基因rs1801131多态性位点的TT、GT、GG基因型和T、G等位基因在NAFLD组与对照组中分布的差异无统计学意义(χ2=1.187,P=0.552;χ2=0.004,P=0.951;P0.05);MTHFR基因rs1801131多态性位点在遗传模型中均与NAFLD无易感性(P0.05)。在NAFLD患者中(男+女),GG基因型携带者的TC水平显著高于TT、GT(GGTTGT)基因型携带者;在男性NAFLD患者中,GG基因型携带者的TC水平显著高于TT、GT(GGTTGT)基因型携带者;在女性NAFLD患者中,GG基因型携带者的LDL-C水平显著高于TT、GT(GGTTGT)基因型携带者,差异均有统计学意义(P0.05),其它临床生化指标在不同基因型之间差异均无统计学意义(P0.05)。7)MTRR基因rs1801394多态性位点的AA、GA、GG基因型和A、G等位基因在NAFLD组与对照组中分布的差异无统计学意义(χ2=1.179,P=0.555;χ2=0.911,P=0.340;P0.05);MTRR基因rs1801394位点在遗传模型中均与NAFLD无易感性(P0.05);在NAFLD患者的生化指标在不同基因型之间差异均无统计学意义(P0.05)。结论:1)在维吾尔族人群中BMI、WC、WHtR与NAFLD的发生有关。肥胖,高血糖,腹性肥胖,高甘油三脂血症,低-高密度脂蛋白血症、高-低密度脂蛋白血症和ALT异常是NAFLD发生的危险因素。2)MTHFR基因rs1801133多态性位点可能与新疆地区维吾尔族人群非酒精性脂肪肝的发生有关联。尤其在女性人群中,携带A等位基因和突变纯合子AA基因的个体发生非酒精性脂肪肝的风险显著升高。MTHFR基因rs1801133多态性位点对FPG、AST、DBP、BMI、WC水平有影响。3)在维吾尔族人群中,MTHFR基因rs1801131多态性位点与NAFLD的发生无相关性。MTHFR基因rs1801131多态性位点对TC、LDL-C水平有影响。4)在维吾尔族人群中,MTRR基因rs1801394多态性位点与NAFLD无相关性。
[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.
【学位授予单位】：新疆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575.5

【相似文献】