eNOS、DDAH2基因多態(tài)性及血漿ADMA、NO水平與云南地區(qū)漢族人群2型糖尿病及2型糖尿病腎病的相關(guān)性研究
發(fā)布時(shí)間：2018-10-10 06:22
【摘要】：[目的]探討eNOS基因4a/b、894G/T多態(tài)性、DDAH2基因-1151A/C多態(tài)性及血漿ADMA、NO水平與2型糖尿病的相關(guān)性。[方法]采用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性(PCR-RFLP)技術(shù)檢測147例健康對照組(NC組)、344例2型糖尿病組(T2DM組)eNOS基因4a/b、894G/T多態(tài)性、DDAH2基因-1151A/C多態(tài)性,應(yīng)用酶聯(lián)免疫吸附法(ELISA)測定血漿ADMA水平,應(yīng)用硝酸還原酶法測定血漿NO水平,比較兩組間基因型、等位基因分布頻率、血漿ADMA水平、NO水平及相關(guān)臨床指標(biāo)。[結(jié)果]①eNOS基因4a/b位點(diǎn)的aa+ab基因型及a等位基因頻率在T2DM組高于NC 組(χ2=13.314,p0.001; χ2 =12.275,p0.001);②eNOS 基因 894G/T位點(diǎn)的GT+TT基因型頻率及T等位基因頻率在T2DM組高于NC組(χ2=6.221,p=0.012; χ2=6.397,p=0.011);③DDAH2基因-1151A/C位點(diǎn)CC基因型頻率在T2DM組高于健康對照組(χ2=6.241,p=0.043); A、C等位基因頻率分布在兩組間無統(tǒng)計(jì)學(xué)差異(χ2=3.149, p=0.061);④血漿ADMA水平在T2DM組(1.19±0.44umol/L)高于NC組(0.60±0.33umol/L),兩組間差異有統(tǒng)計(jì)學(xué)意義(P0.01);⑤血漿 NO 水平在 T2DM 組(57.73 ± 9.67umol/L )低于 NC 組(78.81 ± 15.54 umol/L ),兩組間差異有統(tǒng)計(jì)學(xué)意義(P0.01);⑥血漿ADMA水平與HOMA-IR、收縮壓、舒張壓、低密度脂蛋白、空腹血糖呈正相關(guān)(r分別為0.438、0.354、0.253、0.186、0.381,P 均0.05),與NO呈負(fù)相關(guān)(r為-0.426,P0.05):血漿NO水平與收縮壓、舒張壓、低密度脂蛋白、ADMA呈負(fù)相關(guān)(r分別為-0.318、-0.223、-0.163、-0.426,P 均0.05);⑦eNOS基因4a/b 位點(diǎn):與bb基因型相比,aa+ab基因型攜帶者收縮壓顯著增高(P0.05): eNOS基因894G/T位點(diǎn):與GG基因型相比,GT+TT基因型攜帶者血漿NO水平顯著降低(P0.05); DDAH2基因-1151A/C位點(diǎn):與AC基因型相比,CC基因型攜帶者血漿低密度脂蛋白顯著升高(P0.05);⑧T2DM發(fā)生與否的Logistic回歸顯示,血漿ADMA、年齡、eNOS基因4a/b位點(diǎn)aa基因型、eNOS基因894G/T位點(diǎn)GT基因型可能是T2DM的危險(xiǎn)因素(OR值分別為14.170、1.132、22.441、2.881),血漿NO及高密度脂蛋白可能是T2DM的保護(hù)因素(OR值分別為0.883、0.005)。[結(jié)論]①云南地區(qū)漢族人群存在eNOS基因4a/b、894G/T位點(diǎn)多態(tài)性,DDAH2基因-1151A/C位點(diǎn)多態(tài)性;②eNOS基因4a/b位點(diǎn)aa基因型,eNOS基因894G/T位點(diǎn)GT基因型在云南地區(qū)漢族人群中可能是2型糖尿病的危險(xiǎn)因素;③2型糖尿病患者血漿ADMA水平高于健康對照組、NO水平低于健康對照組,ADMA可能是2型糖尿病的危險(xiǎn)因素,NO可能是2型糖尿病的保護(hù)因素。[目的]探討eNOS 基因4a/b、894G/T多態(tài)性、DDAH2基因-1151A/C多態(tài)性及血漿ADMA、NO水平與2型糖尿病腎病的相關(guān)性。[方法]采用病例-對照研究,將研究對象分為健康對照組(NC組)147例和病例組(T2DM組)344例,并依據(jù)隨機(jī)尿白蛋白/肌酐比值(UACR),將病例組分為T2DM未合并腎病組(DN0組)202例,T2DM合并早期腎病組(DN1組)79例、T2DM合并臨床期腎病組(DN2組)63例、T2DM合并腎病組(DN1+ DN2組)142例,采用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性(PCR-RFLP)技術(shù)檢測所有研究對象的eNOS基因4a/b、894G/T多態(tài)性、DDAH2基因-1151A/C多態(tài)性,比較各組間基因型、等位基因分布頻率、血漿ADMA水平、NO水平及相關(guān)臨床指標(biāo)。[結(jié)果]①eNOS基因4a/b位點(diǎn)aa+ab基因型頻率在DN0組、DN1組、DN2組、DN1+DN2組均高于NC組,DN2組aa+ab基因型頻率高于DN1,DN2組、DN1+DN2組aa+ab基因型頻率均高于DN0組,差異均有統(tǒng)計(jì)學(xué)意義(p0.05);DN1組、DN0組間差異無統(tǒng)計(jì)學(xué)意義(p0.05); eNOS基因4a/b位點(diǎn)的a等位基因頻率在DN0組、DN1組、DN2組、DN1+DN2組均高于健康對照組(P0.05),DN2組、DN1+DN2組a等位基因頻率高于DN0組(P0.05), DN1組與DN0組間,DN2組與DN1組差異無統(tǒng)計(jì)學(xué)意義(p0.05);②eNOS基因894G/T位點(diǎn)GT+TT基因型頻率在DN0組、DN1組、DN2組、DN1+DN2組均高于健康對照組(p0.05); DN0組、DN1組、DN2組、DN1+DN2組間差異無統(tǒng)計(jì)學(xué)意義(P0.05);eNOS基因 894G/T位點(diǎn)T等位基因頻率在DN0組、DN1組、DN2 組、DN1+DN2組均高于NC組(p0.05); DN1+DN2組、DN2組T等位基因頻率高于DN0組(p0.05); DN1 組、DN2 組、DN1+DN2 組間差異無統(tǒng)計(jì)學(xué)意義(P0.05);③DDAH2基因-1151A/C位點(diǎn)中CC基因型頻率在DNO組、DN1組、DN2組、DN1+DN2組均高于健康對照組(p0.05); DNO組、DN1組、DN2組、DN1+DN2組間差異無統(tǒng)計(jì)學(xué)意義(P0.05)。DDAH2-1151A/C中A、C等位基因頻率分布在各組間差異無統(tǒng)計(jì)學(xué)意義(P0.05)。④各組間ADMA水平:DN2組DN1組DN0組,DN1+DN2組DNO組,經(jīng)協(xié)方差分析后,ADMA濃度在各組間的差異仍有統(tǒng)計(jì)學(xué)意義(p0.05);⑤各組間NO水平:DN2組DN1組DNO組,DN1+DN2組DN0組,經(jīng)協(xié)方差分析后,NO濃度在各組間的差異仍有統(tǒng)計(jì)學(xué)意義(p0.05);⑥收縮壓、血肌酐、HbA1C在DN2組高于DN1組高于DNO組,DN1+DN2組高于 DN0 組;FBG、HOMA-IR 在 DN2 組、DN1 組、DN1+DN2 組均高于 DN0組;⑦DN發(fā)生與否的Logistic回歸顯示:收縮壓、FBG、ADMA水平以及eNOS基因4a/b位點(diǎn)aa基因型、eNOS基因894G/T位點(diǎn)GT基因型可能是DN發(fā)生的危險(xiǎn)因素(OR值分別為1.042、1.236、9.938、33.033、1.099),NO水平可能是DN發(fā)生的保護(hù)因素(OR值為0.916); DN發(fā)展與否的Logistic回歸顯示:收縮壓可能是DN發(fā)展的危險(xiǎn)因素(OR值為2.339),NO可能是DN發(fā)展的保護(hù)因素(OR 值為 0.898)。[結(jié)論]①云南地區(qū)漢族人群中,血漿NO水平可能是DN發(fā)生及發(fā)展的保護(hù)因素;②eNOS基因4a/b位點(diǎn)aa基因型、eNOS基因894G/T位點(diǎn)GT基因型可能是DN發(fā)生的危險(xiǎn)因素;③血漿ADMA水平可能是DN發(fā)生的危險(xiǎn)因素,而與DN發(fā)展無相關(guān)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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.1
本文編號：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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.1
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