eNOS、DDAH2基因多态性及血浆ADMA、NO水平与云南地区汉族人群2型糖尿病及2型糖尿病肾病的相关性研究
发布时间：2018-10-10 06:22
【摘要】：[目的]探讨eNOS基因4a/b、894G/T多态性、DDAH2基因-1151A/C多态性及血浆ADMA、NO水平与2型糖尿病的相关性。[方法]采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测147例健康对照组(NC组)、344例2型糖尿病组(T2DM组)eNOS基因4a/b、894G/T多态性、DDAH2基因-1151A/C多态性,应用酶联免疫吸附法(ELISA)测定血浆ADMA水平,应用硝酸还原酶法测定血浆NO水平,比较两组间基因型、等位基因分布频率、血浆ADMA水平、NO水平及相关临床指标。[结果]①eNOS基因4a/b位点的aa+ab基因型及a等位基因频率在T2DM组高于NC 组(χ2=13.314,p0.001; χ2 =12.275,p0.001);②eNOS 基因 894G/T位点的GT+TT基因型频率及T等位基因频率在T2DM组高于NC组(χ2=6.221,p=0.012; χ2=6.397,p=0.011);③DDAH2基因-1151A/C位点CC基因型频率在T2DM组高于健康对照组(χ2=6.241,p=0.043); A、C等位基因频率分布在两组间无统计学差异(χ2=3.149, p=0.061);④血浆ADMA水平在T2DM组(1.19±0.44umol/L)高于NC组(0.60±0.33umol/L),两组间差异有统计学意义(P0.01);⑤血浆 NO 水平在 T2DM 组(57.73 ± 9.67umol/L )低于 NC 组(78.81 ± 15.54 umol/L ),两组间差异有统计学意义(P0.01);⑥血浆ADMA水平与HOMA-IR、收缩压、舒张压、低密度脂蛋白、空腹血糖呈正相关(r分别为0.438、0.354、0.253、0.186、0.381,P 均0.05),与NO呈负相关(r为-0.426,P0.05):血浆NO水平与收缩压、舒张压、低密度脂蛋白、ADMA呈负相关(r分别为-0.318、-0.223、-0.163、-0.426,P 均0.05);⑦eNOS基因4a/b 位点:与bb基因型相比,aa+ab基因型携带者收缩压显著增高(P0.05): eNOS基因894G/T位点:与GG基因型相比,GT+TT基因型携带者血浆NO水平显著降低(P0.05); DDAH2基因-1151A/C位点:与AC基因型相比,CC基因型携带者血浆低密度脂蛋白显著升高(P0.05);⑧T2DM发生与否的Logistic回归显示,血浆ADMA、年龄、eNOS基因4a/b位点aa基因型、eNOS基因894G/T位点GT基因型可能是T2DM的危险因素(OR值分别为14.170、1.132、22.441、2.881),血浆NO及高密度脂蛋白可能是T2DM的保护因素(OR值分别为0.883、0.005)。[结论]①云南地区汉族人群存在eNOS基因4a/b、894G/T位点多态性,DDAH2基因-1151A/C位点多态性;②eNOS基因4a/b位点aa基因型,eNOS基因894G/T位点GT基因型在云南地区汉族人群中可能是2型糖尿病的危险因素;③2型糖尿病患者血浆ADMA水平高于健康对照组、NO水平低于健康对照组,ADMA可能是2型糖尿病的危险因素,NO可能是2型糖尿病的保护因素。[目的]探讨eNOS 基因4a/b、894G/T多态性、DDAH2基因-1151A/C多态性及血浆ADMA、NO水平与2型糖尿病肾病的相关性。[方法]采用病例-对照研究,将研究对象分为健康对照组(NC组)147例和病例组(T2DM组)344例,并依据随机尿白蛋白/肌酐比值(UACR),将病例组分为T2DM未合并肾病组(DN0组)202例,T2DM合并早期肾病组(DN1组)79例、T2DM合并临床期肾病组(DN2组)63例、T2DM合并肾病组(DN1+ DN2组)142例,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测所有研究对象的eNOS基因4a/b、894G/T多态性、DDAH2基因-1151A/C多态性,比较各组间基因型、等位基因分布频率、血浆ADMA水平、NO水平及相关临床指标。[结果]①eNOS基因4a/b位点aa+ab基因型频率在DN0组、DN1组、DN2组、DN1+DN2组均高于NC组,DN2组aa+ab基因型频率高于DN1,DN2组、DN1+DN2组aa+ab基因型频率均高于DN0组,差异均有统计学意义(p0.05);DN1组、DN0组间差异无统计学意义(p0.05); eNOS基因4a/b位点的a等位基因频率在DN0组、DN1组、DN2组、DN1+DN2组均高于健康对照组(P0.05),DN2组、DN1+DN2组a等位基因频率高于DN0组(P0.05), DN1组与DN0组间,DN2组与DN1组差异无统计学意义(p0.05);②eNOS基因894G/T位点GT+TT基因型频率在DN0组、DN1组、DN2组、DN1+DN2组均高于健康对照组(p0.05); DN0组、DN1组、DN2组、DN1+DN2组间差异无统计学意义(P0.05);eNOS基因 894G/T位点T等位基因频率在DN0组、DN1组、DN2 组、DN1+DN2组均高于NC组(p0.05); DN1+DN2组、DN2组T等位基因频率高于DN0组(p0.05); DN1 组、DN2 组、DN1+DN2 组间差异无统计学意义(P0.05);③DDAH2基因-1151A/C位点中CC基因型频率在DNO组、DN1组、DN2组、DN1+DN2组均高于健康对照组(p0.05); DNO组、DN1组、DN2组、DN1+DN2组间差异无统计学意义(P0.05)。DDAH2-1151A/C中A、C等位基因频率分布在各组间差异无统计学意义(P0.05)。④各组间ADMA水平:DN2组DN1组DN0组,DN1+DN2组DNO组,经协方差分析后,ADMA浓度在各组间的差异仍有统计学意义(p0.05);⑤各组间NO水平:DN2组DN1组DNO组,DN1+DN2组DN0组,经协方差分析后,NO浓度在各组间的差异仍有统计学意义(p0.05);⑥收缩压、血肌酐、HbA1C在DN2组高于DN1组高于DNO组,DN1+DN2组高于 DN0 组;FBG、HOMA-IR 在 DN2 组、DN1 组、DN1+DN2 组均高于 DN0组;⑦DN发生与否的Logistic回归显示:收缩压、FBG、ADMA水平以及eNOS基因4a/b位点aa基因型、eNOS基因894G/T位点GT基因型可能是DN发生的危险因素(OR值分别为1.042、1.236、9.938、33.033、1.099),NO水平可能是DN发生的保护因素(OR值为0.916); DN发展与否的Logistic回归显示:收缩压可能是DN发展的危险因素(OR值为2.339),NO可能是DN发展的保护因素(OR 值为 0.898)。[结论]①云南地区汉族人群中,血浆NO水平可能是DN发生及发展的保护因素;②eNOS基因4a/b位点aa基因型、eNOS基因894G/T位点GT基因型可能是DN发生的危险因素;③血浆ADMA水平可能是DN发生的危险因素,而与DN发展无相关性。
[Abstract]:[Objective] To investigate the association between the polymorphism of gene 4a/ b, 894G/ T polymorphism, DDAH2 gene-1151A/ C polymorphism and plasma ADMA, NO level and type 2 diabetes mellitus. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect 147 healthy controls (NC group), 344 patients with type 2 diabetes mellitus (T2DM), 4a/ b, 894G/ T polymorphism, DDAH2 gene-1151A/ C polymorphism. Plasma levels of ADMA were determined by enzyme-linked immunosorbent assay (ELISA). Plasma NO levels were determined by nitric acid reductase method.[Results] The genotype frequency and allele frequency of aa + ab genotype and a allele frequency were higher in T2DM group than those in NC group (group 2 = 13. 314, T. 001; Bit 2 = 12. 275, T. 001). The frequency of GT + TT genotype and T allele frequency were higher in T2DM group than in NC group (group 2 = 6.221, p = 0.0012; Table 2 = 6.397, p = 0.0011). The genotype frequencies of DDAH2 gene-1151A/ C locus were higher in T2DM group than in healthy control group (group 2 = 6. 241, p = 0.043). The frequency distribution of allele A and C was not statistically different between the two groups (Table 2 = 3.149, p = 0.061). The level of ADMA in plasma was higher than that of NC group (0. 60 vs 0. 33umol/ L) in T2DM group (1.190.44umol/ L). There was a statistically significant difference between the two groups (P0.01); the plasma NO level in the two groups was lower than that of the NC group (7.73/ 9.67umol/ L) than that in the NC group (78. 81, 15.54 umol/ L). The difference between the two groups was statistically significant (P0.01); the plasma ADMA level in the two groups was correlated with HOMA-IR, systolic blood pressure, diastolic blood pressure, and low density lipoprotein. There was a negative correlation between plasma NO level and systolic blood pressure, diastolic blood pressure, low density lipoprotein and ADMA (r =-0.318,-0.223,-0.163,-0.426, P 0.05). Compared with the bb genotype, the systolic blood pressure of the AA + AB genotype was significantly higher than that of the GG genotype (P <0.05). Compared with the GG genotype, the plasma NO level of the GT + TT genotype was significantly decreased (P0.05). There was a significant increase in plasma low density lipoprotein in CC genotype carriers (P <0.05). Logistic regression showed that the genotype of ADMA, age, gene 4a/ b in plasma, and the genotype of gene 894G/ T in plasma could be a risk factor for T2DM (OR values were 14. 170, 1. 132, 22. 441, 2. 881, respectively). Plasma NO and high density lipoprotein may be a protective factor for T2DM (OR values are 0. 883, 0. 005, respectively).[Conclusion] The polymorphism of gene 4a/ b, 894G/ T locus, the polymorphism of DDAH2 gene-1151A/ C locus in Han population of Yunnan region, and the genotype of gene 4a/ b and the gene 894G/ T locus were probably the risk factors of type 2 diabetes in the Han population of Yunnan region. The level of ADMA in patients with type 2 diabetes is higher than that of healthy control group. The level of NO is lower than that of healthy control group. ADMA may be a risk factor for type 2 diabetes, and NO may be a protective factor for type 2 diabetes.[Objective] To investigate the association between the polymorphism of gene 4a/ b, 894G/ T polymorphism, DDAH2 gene-1151A/ C polymorphism and plasma ADMA, NO level and type 2 diabetic nephropathy.[Methods] In case-control study, the subjects were divided into two groups: healthy control group (NC group), 147 cases and case group (T2DM group) 344 cases. There were 79 cases of T2DM complicated with early nephropathy (DN1 group), 63 cases of T2DM complicated with clinical stage nephropathy group (DN2 group), and 142 cases of T2DM complicated nephrosis group (DN1 + DN2 group). The gene 4a/ b and 894G/ T polymorphism of all subjects were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. DDAH2 gene-1151A/ C polymorphism was used to compare genotype, allele distribution frequency, plasma ADMA level, NO level and relevant clinical index in each group.[Results] The gene 4a/ b locus aa + ab genotype was higher in DN0 group, DN1 group, DN2 group, DN1 + DN2 group higher than NC group, and the frequency of AA + ab in DN2 group was higher than that of DN1, DN2 group, DN1 + DN2 group, and the frequency of AA + ab genotype was higher than that of DN0 group (P0.05). There was no significant difference between DN0 group and DN0 group (P0.05). The frequency of A allele was higher in DN0 group, DN1 group, DN2 group, DN1 + DN2 group than in healthy control group (P0.05), DN2 group, DN1 + DN2 group a allele frequency was higher than DN0 group (P0.05), DN1 group and DN0 group. There was no significant difference between DN2 group and DN1 group (P 0.05). The frequency of GT + TT genotype at 894G/ T locus was higher in DN0 group, DN1 group, DN2 group, DN1 + DN2 group than in healthy control group (P0.05), and there was no significant difference between DN0 group, DN1 group, DN2 group and DN1 + DN2 group (P0.05). The frequency of T allele at 894G/ T locus was higher in DN0 group, DN1 group, DN2 group, DN1 + DN2 group higher than NC group (P0.05). The frequencies of CC genotype were higher in DNO group, DN1 group, DN2 group, DN1 + DN2 group in DNO group, DN1 group, DN2 group, DN1 + DN2 group, but there was no significant difference between DNO group, DN1 group, DN2 group and DN1 + DN2 group (P0.05). The levels of ADMA in each group: DN0 group, DN1 + DN2 group DNO group in DN2 group and DNO group of DN1 + DN2 group were still statistically significant after covariance analysis (P0.05). The difference of NO concentration between groups was still statistically significant (P 0.05); systolic blood pressure, blood viscosity, HbA1C were higher in DN2 group than DNO group, DN1 + DN2 group was higher than DN0 group; FBG, HOMA-IR were higher than DN0 group in DN2 group, DN1 group, DN1 + DN2 group, and Logistic regression showed that systolic blood pressure, FBG, The gene 894G/ T locus was the risk factor for DN (OR = 1. 029, 1. 236, 9. 938, 33. 033, 1. 099). The level of NO may be the protective factor of DN (OR value is 0. 916). The Logistic regression of DN development indicates that: The systolic blood pressure may be a risk factor for DN development (OR value is 2.339), and NO may be a protective factor for DN development (OR value is 0. 98).[Conclusion] In the Han population of Yunnan region, the level of plasma NO may be the protective factor of DN development and development. The genotype of the gene 4a/ b and the gene 894G/ T locus are likely to be the risk factors for DN. The level of ADMA in plasma can be a risk factor for DN. There was no correlation with DN development.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1
本文编号：2260965
[Abstract]:[Objective] To investigate the association between the polymorphism of gene 4a/ b, 894G/ T polymorphism, DDAH2 gene-1151A/ C polymorphism and plasma ADMA, NO level and type 2 diabetes mellitus. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect 147 healthy controls (NC group), 344 patients with type 2 diabetes mellitus (T2DM), 4a/ b, 894G/ T polymorphism, DDAH2 gene-1151A/ C polymorphism. Plasma levels of ADMA were determined by enzyme-linked immunosorbent assay (ELISA). Plasma NO levels were determined by nitric acid reductase method.[Results] The genotype frequency and allele frequency of aa + ab genotype and a allele frequency were higher in T2DM group than those in NC group (group 2 = 13. 314, T. 001; Bit 2 = 12. 275, T. 001). The frequency of GT + TT genotype and T allele frequency were higher in T2DM group than in NC group (group 2 = 6.221, p = 0.0012; Table 2 = 6.397, p = 0.0011). The genotype frequencies of DDAH2 gene-1151A/ C locus were higher in T2DM group than in healthy control group (group 2 = 6. 241, p = 0.043). The frequency distribution of allele A and C was not statistically different between the two groups (Table 2 = 3.149, p = 0.061). The level of ADMA in plasma was higher than that of NC group (0. 60 vs 0. 33umol/ L) in T2DM group (1.190.44umol/ L). There was a statistically significant difference between the two groups (P0.01); the plasma NO level in the two groups was lower than that of the NC group (7.73/ 9.67umol/ L) than that in the NC group (78. 81, 15.54 umol/ L). The difference between the two groups was statistically significant (P0.01); the plasma ADMA level in the two groups was correlated with HOMA-IR, systolic blood pressure, diastolic blood pressure, and low density lipoprotein. There was a negative correlation between plasma NO level and systolic blood pressure, diastolic blood pressure, low density lipoprotein and ADMA (r =-0.318,-0.223,-0.163,-0.426, P 0.05). Compared with the bb genotype, the systolic blood pressure of the AA + AB genotype was significantly higher than that of the GG genotype (P <0.05). Compared with the GG genotype, the plasma NO level of the GT + TT genotype was significantly decreased (P0.05). There was a significant increase in plasma low density lipoprotein in CC genotype carriers (P <0.05). Logistic regression showed that the genotype of ADMA, age, gene 4a/ b in plasma, and the genotype of gene 894G/ T in plasma could be a risk factor for T2DM (OR values were 14. 170, 1. 132, 22. 441, 2. 881, respectively). Plasma NO and high density lipoprotein may be a protective factor for T2DM (OR values are 0. 883, 0. 005, respectively).[Conclusion] The polymorphism of gene 4a/ b, 894G/ T locus, the polymorphism of DDAH2 gene-1151A/ C locus in Han population of Yunnan region, and the genotype of gene 4a/ b and the gene 894G/ T locus were probably the risk factors of type 2 diabetes in the Han population of Yunnan region. The level of ADMA in patients with type 2 diabetes is higher than that of healthy control group. The level of NO is lower than that of healthy control group. ADMA may be a risk factor for type 2 diabetes, and NO may be a protective factor for type 2 diabetes.[Objective] To investigate the association between the polymorphism of gene 4a/ b, 894G/ T polymorphism, DDAH2 gene-1151A/ C polymorphism and plasma ADMA, NO level and type 2 diabetic nephropathy.[Methods] In case-control study, the subjects were divided into two groups: healthy control group (NC group), 147 cases and case group (T2DM group) 344 cases. There were 79 cases of T2DM complicated with early nephropathy (DN1 group), 63 cases of T2DM complicated with clinical stage nephropathy group (DN2 group), and 142 cases of T2DM complicated nephrosis group (DN1 + DN2 group). The gene 4a/ b and 894G/ T polymorphism of all subjects were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. DDAH2 gene-1151A/ C polymorphism was used to compare genotype, allele distribution frequency, plasma ADMA level, NO level and relevant clinical index in each group.[Results] The gene 4a/ b locus aa + ab genotype was higher in DN0 group, DN1 group, DN2 group, DN1 + DN2 group higher than NC group, and the frequency of AA + ab in DN2 group was higher than that of DN1, DN2 group, DN1 + DN2 group, and the frequency of AA + ab genotype was higher than that of DN0 group (P0.05). There was no significant difference between DN0 group and DN0 group (P0.05). The frequency of A allele was higher in DN0 group, DN1 group, DN2 group, DN1 + DN2 group than in healthy control group (P0.05), DN2 group, DN1 + DN2 group a allele frequency was higher than DN0 group (P0.05), DN1 group and DN0 group. There was no significant difference between DN2 group and DN1 group (P 0.05). The frequency of GT + TT genotype at 894G/ T locus was higher in DN0 group, DN1 group, DN2 group, DN1 + DN2 group than in healthy control group (P0.05), and there was no significant difference between DN0 group, DN1 group, DN2 group and DN1 + DN2 group (P0.05). The frequency of T allele at 894G/ T locus was higher in DN0 group, DN1 group, DN2 group, DN1 + DN2 group higher than NC group (P0.05). The frequencies of CC genotype were higher in DNO group, DN1 group, DN2 group, DN1 + DN2 group in DNO group, DN1 group, DN2 group, DN1 + DN2 group, but there was no significant difference between DNO group, DN1 group, DN2 group and DN1 + DN2 group (P0.05). The levels of ADMA in each group: DN0 group, DN1 + DN2 group DNO group in DN2 group and DNO group of DN1 + DN2 group were still statistically significant after covariance analysis (P0.05). The difference of NO concentration between groups was still statistically significant (P 0.05); systolic blood pressure, blood viscosity, HbA1C were higher in DN2 group than DNO group, DN1 + DN2 group was higher than DN0 group; FBG, HOMA-IR were higher than DN0 group in DN2 group, DN1 group, DN1 + DN2 group, and Logistic regression showed that systolic blood pressure, FBG, The gene 894G/ T locus was the risk factor for DN (OR = 1. 029, 1. 236, 9. 938, 33. 033, 1. 099). The level of NO may be the protective factor of DN (OR value is 0. 916). The Logistic regression of DN development indicates that: The systolic blood pressure may be a risk factor for DN development (OR value is 2.339), and NO may be a protective factor for DN development (OR value is 0. 98).[Conclusion] In the Han population of Yunnan region, the level of plasma NO may be the protective factor of DN development and development. The genotype of the gene 4a/ b and the gene 894G/ T locus are likely to be the risk factors for DN. The level of ADMA in plasma can be a risk factor for DN. There was no correlation with DN development.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1
【参考文献】
相关期刊论文 前10条
1 张舒媛;时晓娟;徐暾海;刘铜华;;糖尿病肾病不同分期防治研究进展[J];中医药导报;2016年02期
2 汪会琴;胡如英;武海滨;俞敏;;2型糖尿病报告发病率研究进展[J];浙江预防医学;2016年01期
3 石柔;杨晶晶;刘华;陈洪艳;雷又鸣;宋滇平;;DDAH2基因-449G/C多态性及ADMA水平与2型糖尿病合并动脉粥样硬化的相关性[J];中国动脉硬化杂志;2015年09期
4 田骆冰;秦江媛;刘冠华;甄艳凤;张禾伟;孙雪玲;张谷月;张丹丹;房辉;;胰岛素受体底物-1、内皮型一氧化氮合酶与胰岛素抵抗、糖尿病下肢血管病变及糖尿病足发病关系的临床研究[J];中国糖尿病杂志;2014年12期
5 臧强;郭维康;王丽妍;刘文虎;;ADMA可以通过自噬引起内皮细胞死亡[J];临床和实验医学杂志;2014年13期
6 陈振宇;汤礼军;;多元醇通路与氧化应激在糖尿病慢性并发症中的关系[J];西南军医;2014年03期
7 张顺芝;孙吉;刘丽华;陈磊;陈小平;;DDAH2启动子区-1150C/A多态性与中国汉族人群冠心病的遗传易感性研究[J];现代生物医学进展;2014年05期
8 周燕琼;金成;张英;;晚期糖基化终末产物(AGEs)形成途径、检测方法和抑制手段研究进展[J];中国食品学报;2013年06期
9 张美红;王仁萍;季晓云;刘丹;毛拥军;;eNOS基因多态性与老年左心室舒张功能不全相关性[J];青岛大学医学院学报;2013年02期
10 杨改清;胥丽霞;刘举;吴孟娇;李晓昶;;内皮型一氧化氮合成酶基因G298A、-786T>C多态性与缺血性脑卒中的关系[J];中国实用神经疾病杂志;2012年24期
相关博士学位论文 前1条
1 刘永生;内皮型一氧化氮合酶基因多态性与原发性高血压发病相关性的研究[D];吉林大学;2014年
相关硕士学位论文 前1条
1 黄湘壹;高血压患者NO、eNOS及ADMA水平及其与急性心肌梗死的关系[D];南华大学;2015年
，本文编号：2260965
本文链接：https://www.wllwen.com/kejilunwen/jiyingongcheng/2260965.html
最近更新
教材专著
