CUBN基因单核苷酸多态性与2型糖尿病合并肾病的关联研究

发布时间：2018-06-09 20:40

本文选题：CUBN基因 + 单核苷酸多态性　；参考：《长江大学》2017年硕士论文

【摘要】：背景:糖尿病肾病(diabetic kidney disease,DKD)是糖尿病(diabetes mellitus,DM)严重慢性血管并发症之一,已成为引起终末期肾病(End Stage Renal Disease,ESRD)及糖尿病病死率增加的重要因素。目前的研究表明,长期的糖代谢紊乱和遗传因素是引起DKD的主要原因。近来,在欧洲和美国进行的包括63153人的全基因组分析分析研究(genome-wide association studies,GWAS)发现,内因子-维生素B12复合体的受体基因(receptor gene of internal factor vitamin B12 complex,CUBN)是DKD的一个候选基因。CUBN基因变异在随后另两项在欧美大样本人群研究中再次证实与DKD相关。然而,CUBN基因变异与DKD易感性在中国人群中的关联性却未有研究。由于不同地域和种族在DKD的遗传和表型差异,不同人群中单核苷酸多态性(singlenucleotide polymorphisms,SNP)位点的各等位基因频率分布也不同,因此有必要在中国人群中针对CUBN基因进行群体关联研究。目的:1.探讨CUBN基因位点rs1801239(T→C)变异和rs10795433(A/C)多态性在中国汉族人群2型搪尿病(type 2 diabetes mellitus,T2DM)中的分布情况。2.探讨CUBN基因位点rs1801239(T→C)变异和rs10795433(A/C)多态性与DKD易感性的关系。3.探讨DKD发生的相关危险因素。方法:应用基质辅助激光解析/电离飞行时间质谱(matrix-assisted laserdesorption ionization time-of-flight mass spectrometry,MALDI-TOF-MS)测序分型的方法,检测198例中国汉族人群T2DM患者中CUBN基因位点rs1801239(T→C)和rs10795433(A/C)位点的分布情况。根据尿微白蛋白排泄率(urinary albuminuric excretion rate,UAER),将研究对象分为两组:病例组糖尿病肾病(DKD+)与对照组糖尿病不伴肾病(DKD-)组。对两组各项临床变量、各等位基因频率、基因型频率、进行比较分析,使用SPSS16.0统计软件对上述各项变量进行统计学处理。结果:1.两组临床资料分析:本次试验共纳入病例600例,其中DKD+334例,DKD-组266例,两组年龄分别为60.61±12.16岁和59.36±10.43岁。DKD+组糖尿病的病程、甘油三酯水平、高血压的发生率、收缩压、舒张压及视网膜病变的发生率高于DKD-组,DKD+组e GFR低于DKD-组。2.CUBN基因两变异位点的频率分布:CUBN rs1801239(T→C)(突变),1人基因型为CT,599人为TT,表明纳入人群总体无变异。CUBN rs10795433 A/C(SNP)基因型实测值与预测值之间差异均无统计学意义(P0.05),两组基因型分布符合Hardy-Weinberg遗传平衡定律;DKD+组和DKD-组等位基因及基因型频率的分布差异均无统计学意义均(P0.05)。3.DKD相关因素的logistic回归分析:rs10795433 A等位或C等位基因的表达不是DKD的危险因素。糖尿病病程、甘油三酯、高血压发生率、收缩压、舒张压、视网膜病变的发生率增加DKD的发生,而e GFR的增加为其保护因素。结论:1.本实验选取的样本,CUBN rs1801239(T→C)总体无变异;CUBN rs10795433(A/C)基因型分布符合Hardy-Weinberg遗传平衡定律。2.本研究选取的样本,CUBN基因位点rs1801239(T→C)变异和rs10795433(A/C)多态性与DKD不存在关联性,但cubilin受体与蛋白尿的密切关系,需进一步扩在更多人群中对这两位点进行研究。3.本研究选取的样本,logistic回归分析表明,rs10795433 A等位或C等位基因的表达不是DKD的危险因素。糖尿病病程、甘油三酯、高血压发生率、收缩压、舒张压、视网膜病变的发生率增加DKD的发生,而e GFR的增加为其保护因素。表明对DKD有上述风险的患者需控制血脂、血压,定期检查眼底及避免使用肾毒性药物。
[Abstract]:Background: diabetic kidney disease (DKD) is one of the serious and chronic vascular complications of diabetes mellitus (DM). It has become an important factor causing the death rate of end-stage renal disease (End Stage Renal Disease, ESRD) and diabetes. Main reasons. Recently, genome-wide association studies (GWAS), including 63153 people in Europe and the United States, found that the receptor gene of the endogenous factor vitamin B12 complex (receptor gene of internal factor vitamin B12) is a candidate gene mutation in the following The other two were reconfirmed with DKD in large population studies in Europe and America. However, the correlation between the CUBN gene mutation and DKD susceptibility in Chinese population was not studied. Because of the genetic and phenotypic differences in different regions and races in DKD, the alleles of the single nucleotide polymorphisms (singlenucleotide polymorphisms, SNP) loci of different populations were in different populations. The distribution of gene frequency is also different, so it is necessary to study the Group Association for CUBN gene in Chinese population. Objective: 1. to explore the distribution of CUBN gene locus rs1801239 (T to C) variation and rs10795433 (A/C) polymorphism in Chinese Han population type 2 enamel disease (type 2 diabetes mellitus, T2DM) (T to C) variation and the relationship between rs10795433 (A/C) polymorphism and DKD susceptibility.3. explore the related risk factors of DKD occurrence. Methods: the method of using matrix assisted laser desorption / ionization time of flight mass spectrometry (matrix-assisted LaserDesorption ionization time-of-flight mass) sequencing and classification method, 198 Chinese Han cases were detected. The distribution of the CUBN gene locus rs1801239 (T to C) and rs10795433 (A/C) loci in T2DM patients were divided into two groups according to the urinary microalbumin excretion rate (urinary albuminuric excretion rate, UAER). The allele frequency and genotype frequency were compared and analyzed with SPSS16.0 statistical software. Results: 1. two groups of clinical data were analyzed: 600 cases were included in this trial, including DKD+334, group DKD-, 266, and the two groups were 60.61 + 12.16 and 59.36 + 10.43 years old. The incidence of triglyceride, triglyceride, hypertension, systolic pressure, diastolic pressure and retinopathy was higher than that of the DKD- group. The e GFR in group DKD+ was lower than that in group DKD-, the frequency distribution of.2.CUBN gene two ectopic sites: CUBN rs1801239 (T to C) (mutation), the 1 genotype was CT, and 599 people were TT. There was no significant difference between the measured values and the predicted values (P0.05). The distribution of genotype distribution in the two groups accords with the Hardy-Weinberg's law of genetic balance; the distribution of alleles and genotype frequencies of DKD+ and DKD- groups have no statistical significance (P0.05).3.DKD related factors in logistic regression analysis: rs10795433 A alleles or C alleles Expression was not a risk factor for DKD. The course of diabetes, triglyceride, the incidence of hypertension, systolic pressure, diastolic pressure, and the incidence of retinopathy increased DKD, and the increase of E GFR was the protective factor. Conclusion: 1. samples selected from this experiment, CUBN rs1801239 (T to C) were generally not variant; CUBN rs10795433 (A/C) genotype distribution accords with Har Dy-Weinberg genetic equilibrium law.2. selected samples, CUBN locus rs1801239 (T to C) variation and rs10795433 (A/C) polymorphism are not associated with DKD, but the close relationship between the Cubilin receptor and proteinuria needs to be further expanded in more population to study the two loci.3. this study selected samples, logistic regression analysis The expression of rs10795433 A allele or C allele is not a risk factor for DKD. The course of diabetes, triglyceride, the incidence of hypertension, systolic pressure, diastolic pressure, and the incidence of retinopathy increase DKD, and the increase of E GFR is a protective factor. It is indicated that patients with the risk of DKD have to control blood lipids, blood pressure, and regular examination of the eyes. To avoid the use of nephrotoxic drugs.
【学位授予单位】：长江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R692.9

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