SAA1水平及其基因rs12218多态性与2型糖尿病及糖尿病肾病的相关性研究
发布时间：2018-07-14 08:07
【摘要】：目的：探讨血清淀粉样蛋白Al(serum amyloid Al,SAA1)水平及其rs12218基因多态性与2型糖尿病(T2DM)及糖尿病肾病(DN)的相关性。 研究方法：选取延边地区正常对照组(normal glucose tolerant, NGT)50例,T2DM组215例。T2DM组再根据尿蛋白排泄率(UAER)进一步分为糖尿病无肾病组(NDN组)65例,糖尿病肾病组(DN组)140例。采用酶联免疫法(ELISA)测定样本血清的SAA1水平。用荧光测序法测定基因序列,将基因组DNA进行扩增、纯化后进行DNA测序,S anger双脱氧链终止法基因分型。采用放射免疫法测定尿液中白蛋白的浓度。用SPSS17.0统计软件进行数据的统计分析。计量资料以均数±标准差(x±s)表示,组间比较行单因素方差分析。采用Spearman相关分析对SAA1与临床各生化指标进行相关分析。组间基因型及等位基因频率比较采用Pearson's χ2检验。采用Logistic回归分析筛选DN病变的危险因素。 结果：1.NDN组SAA1水平高于DN组,并且DN组SAA1水平高于NDN组,有统计学差异(P0.05)。 2.NDN组和DN组的SBP、DBP、FPG、2hPG、HbA1c、CREA指数高于NGT组,有统计学差异(P0.05)。且DN组的SBP、DBP、FPG、2hPG、HbAlc、CREA指数高于NDN组,有统计学差异(P0.05)。 3.SAA1与年龄、病程、FPG、2hPG、HbAlc、CREA呈明显正相关,有统计学差异(P0.05)。 4.延边朝鲜族、汉族人群的SAA1基因rs12218的等位基因频率分布与HapMap数据库(SS40072010)的欧洲人(CEU)、中国北京汉族人(HCB)、日本东京人(JPT)和非洲约鲁巴人(YRI)进行比较,结果显示：延边朝鲜族和汉族人群的rs12218(A)位点等位基因频率无民族差异(p0.05),延边朝鲜族rs12218-A等位基因频率显著高于CEU (p0.01)。与HCB、JPT无统计学差异。在延边汉族rs12218-A等位基因频率与CEU、HCB、JPT比较,均无统计学差异(p0.05) 5.rs12218-G等位基因频率在NDN组中出现的频率高于NGT组(32.3%16.0%,P=0.045),并且rs12218-G等位基因频率在DN组中出现的频率高于NDN组(33.2%32.3%,P=0.046)。在显性模型(AG+GG:AA)分析中,携带AG+GG基因型患NDN的风险是NGT组的1.673倍(P=0.04, OR=1.673,95%CI:0.76-3.69),'并且在显性模型(AG+GG:AA)分析中,携带AG+GG基因型患DN的风险是NDN1.46倍(P=0.046, OR=1.673,95%CI:0.67-3.35) 6.NGT组、NDN组、DN组各组内AG+GG基因型者SAA1水平明显高于AA基因型者SAA1水平,均有统计学差异(P0.05)。 7.rs12218多态基因型在NGT、NDN、DN各组内临床指标未发现存在显著性差异(P0.05);rs12218多态基因型的显性模式在NGI、NDN、DN各组内临床指标未发现存在显著性差异(P0.05)；rs12218多态基因型的隐性模式在NGT、NDN、DN各组内临床指标未发现存在显著性差异(P0.05)。 8.PBG、SAA1水平、AG+GG基因型为DN的危险因素。 结论： 1.SAA1水平与T2DM及DN呈正相关。 2.SAA1基因rs12218-G等位基因可能是DN的易感基因。 3.SAA1基因rs12218位点存在种族差异。
[Abstract]:Objective: to investigate the relationship between serum amyloid Al (serum amyloid AlanSAA1 and rs12218 gene polymorphisms in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods: according to urinary protein excretion rate (UAER), 50 cases of normal control group (normal glucose tolerant,) and 215 cases of T2DM group were divided into diabetic nephropathy group (n = 65) and diabetic nephropathy group (DN group) (n = 140) according to urinary protein excretion rate (UAER). The level of SAA1 in serum was measured by enzyme-linked immunosorbent assay (Elisa). The gene sequence was sequenced by fluorescence sequencing, and the genomic DNA was amplified. After purification, the S anger dideoxy chain termination method was used for genotyping. The concentration of albumin in urine was determined by radioimmunoassay. SPSS 17.0 statistical software was used to analyze the data. The measurement data were expressed as mean 卤standard deviation (x 卤s), and single factor analysis of variance (ANOVA) was performed. Spearman correlation analysis was used to analyze the correlation between SAA1 and clinical biochemical indexes. The frequencies of genotypes and alleles were compared by Pearson's 蠂 2 test. Logistic regression analysis was used to screen the risk factors of DN. Results 1. The level of SAA1 in NDN group was higher than that in DN group, and the level of SAA1 in DN group was higher than that in NDN group (P0.05). Moreover, the CREA index of SBPnDBPnf2hPG2hPGHbAlcCU in DN group was significantly higher than that in NDN group (P0.05). 3. SAA1 was positively correlated with age and course of disease (P0.05), and there was significant difference in CREA (P0.05). The allele frequency distribution of SAA1 gene rs12218 in Yanbian Korean and Han population was compared with that of European (CEU) in HapMap database (SS40072010), Han nationality (Chinese) in Beijing, Japanese (Tokyo) and African Yoruba (YRI). The results showed that the frequency of rs12218 (A) allele in Yanbian Korean and Han nationality was not different (p0.05), but the frequency of rs12218-A allele in Yanbian Korean was significantly higher than that of CEU (p0.01). There was no statistical difference between JPT and HCB. The frequency of rs12218-A allele in Yanbian Han nationality was higher than that in NGT group (p 0.05), and the frequency of rs12218-G allele in DN group was higher than that in NDN group (33.23.3% P0.046). In the AG GG: AA analysis, the risk of NDN carrying the AG GG genotype was 1.673 times higher than that of the NGT group (P0.04, OR1.67395 CI: 0.76-3.69) 'and in the AG GG: AA analysis, the risk of NDN was 1.673 times higher than that of the NGT group (P0.04, OR1.67395 CI: 0.76-3.69)' and in the AG GG: AA analysis, The risk of DN with AG GG genotype was 1.46 times higher than that of NDN genotype (P0.046, OR1 1.67395 CI0.67-3.35) 6.The SAA1 level of AG GG genotype in DN group was significantly higher than that in AA genotype group in NGT group. There was no significant difference in the clinical indexes of 7.rs12218 polymorphism genotypes (P0.05). (P0.05) the dominant pattern of rs12218 polymorphism genotype was not found in the clinical indexes of NGTN NDNNNNDN groups (P0.05). There was no significant difference in the clinical parameters of rs12218 polymorphism genotype among the three groups (P0.05). 8. PBGG SAA1 level and AG GG genotype were the risk factors of DN. Conclusion: 1. SAA1 level is positively correlated with T2DM and DN. 2. SAA1 rs12218-G allele may be the susceptible gene of DN. 3. There are racial differences in rs12218 loci of SAA1 gene.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R587.2;R692
本文编号：2121013
[Abstract]:Objective: to investigate the relationship between serum amyloid Al (serum amyloid AlanSAA1 and rs12218 gene polymorphisms in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods: according to urinary protein excretion rate (UAER), 50 cases of normal control group (normal glucose tolerant,) and 215 cases of T2DM group were divided into diabetic nephropathy group (n = 65) and diabetic nephropathy group (DN group) (n = 140) according to urinary protein excretion rate (UAER). The level of SAA1 in serum was measured by enzyme-linked immunosorbent assay (Elisa). The gene sequence was sequenced by fluorescence sequencing, and the genomic DNA was amplified. After purification, the S anger dideoxy chain termination method was used for genotyping. The concentration of albumin in urine was determined by radioimmunoassay. SPSS 17.0 statistical software was used to analyze the data. The measurement data were expressed as mean 卤standard deviation (x 卤s), and single factor analysis of variance (ANOVA) was performed. Spearman correlation analysis was used to analyze the correlation between SAA1 and clinical biochemical indexes. The frequencies of genotypes and alleles were compared by Pearson's 蠂 2 test. Logistic regression analysis was used to screen the risk factors of DN. Results 1. The level of SAA1 in NDN group was higher than that in DN group, and the level of SAA1 in DN group was higher than that in NDN group (P0.05). Moreover, the CREA index of SBPnDBPnf2hPG2hPGHbAlcCU in DN group was significantly higher than that in NDN group (P0.05). 3. SAA1 was positively correlated with age and course of disease (P0.05), and there was significant difference in CREA (P0.05). The allele frequency distribution of SAA1 gene rs12218 in Yanbian Korean and Han population was compared with that of European (CEU) in HapMap database (SS40072010), Han nationality (Chinese) in Beijing, Japanese (Tokyo) and African Yoruba (YRI). The results showed that the frequency of rs12218 (A) allele in Yanbian Korean and Han nationality was not different (p0.05), but the frequency of rs12218-A allele in Yanbian Korean was significantly higher than that of CEU (p0.01). There was no statistical difference between JPT and HCB. The frequency of rs12218-A allele in Yanbian Han nationality was higher than that in NGT group (p 0.05), and the frequency of rs12218-G allele in DN group was higher than that in NDN group (33.23.3% P0.046). In the AG GG: AA analysis, the risk of NDN carrying the AG GG genotype was 1.673 times higher than that of the NGT group (P0.04, OR1.67395 CI: 0.76-3.69) 'and in the AG GG: AA analysis, the risk of NDN was 1.673 times higher than that of the NGT group (P0.04, OR1.67395 CI: 0.76-3.69)' and in the AG GG: AA analysis, The risk of DN with AG GG genotype was 1.46 times higher than that of NDN genotype (P0.046, OR1 1.67395 CI0.67-3.35) 6.The SAA1 level of AG GG genotype in DN group was significantly higher than that in AA genotype group in NGT group. There was no significant difference in the clinical indexes of 7.rs12218 polymorphism genotypes (P0.05). (P0.05) the dominant pattern of rs12218 polymorphism genotype was not found in the clinical indexes of NGTN NDNNNNDN groups (P0.05). There was no significant difference in the clinical parameters of rs12218 polymorphism genotype among the three groups (P0.05). 8. PBGG SAA1 level and AG GG genotype were the risk factors of DN. Conclusion: 1. SAA1 level is positively correlated with T2DM and DN. 2. SAA1 rs12218-G allele may be the susceptible gene of DN. 3. There are racial differences in rs12218 loci of SAA1 gene.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R587.2;R692
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