血浆尿酸水平、GCKR基因多态性与2型糖尿病的关联性研究
发布时间：2018-08-16 15:43
【摘要】：第一部分血浆尿酸水平与2型糖尿病的关联性目的:探讨血浆UA水平与T2DM的关联性。方法:研究对象为利用OGTT试验进行糖尿病筛检的人群。根据WHO 1999年推荐的诊断标准,将研究对象分为正常对照组、IGR和T2DM组。利用全自动生化分析仪(尿酸酶-过氧化物酶法)检测血浆UA的浓度。结果:本研究共纳入3685名研究对象,其中T2DM病例1322名,IGR病例775名,正常对照1588名;男性分别占59.91%、63.10%和58.06%。对照组、IGR组和T2DM组血浆UA的浓度分别为4.69(3.91-5.72)mg/dL、5.09(4.07-6.18)mg/dL和5.22(4.26-6.27)mg/dL,与对照组相比IGR组和T2DM组的血浆UA浓度显著升高(P0.001)。按照对照组尿酸的分布,将血浆UA水平分为三组,校正年龄、性别、BMI、DM家族史和高血压等混杂因素后结果显示:血浆UA水平高浓度组的与低浓度组相比IGR和T2DM的患病风险分别增加了56.1%(OR=1.561(1.206-2.020),P=0.072)和23.6%(OR=1.236(0.995-1.535),P=0.056)。对血浆UA水平与T2DM的关联按性别进行分层分析,按血浆UA水平的分布分别分为四分位组:校正以上混杂因素后,血浆UA水平与T2DM患病风险之间的关联呈现U型曲线的趋势。随尿酸水平的升高,T2DM的患病风险呈现先降低后升高。女性尿酸水平高四分位组的与低四分位相比,患T2DM和IGR+T2DM的OR值分别为2.614(1.805-3.787)和2.842(2.022-3.993)。结论:血浆UA水平可显著增加T2DM的患病风险。在性别分层分析中,血浆ua水平与t2dm患病风险之间的关联呈现u型曲线的趋势。女性尿酸水平(3.95-7.00mg/dl)高四分位组与低四分位组相比可显著增加t2dm的患病风险。第二部分gckr基因多态性与2型糖尿病的关联性目的:探讨gckr基因rs780094位点基因多态性与t2dm和igr患病风险的关联性。方法:研究对象同第一部分。采用taqman探针荧光定量pcr法,对gckr基因rs780094位点进行基因分型。结果:对照组、igr组和t2dm组人群gckrrs780094位点的最小等位基因(c等位基因)频率分别为:48.7%、49.0%和51.3%。校正年龄、性别、bmi、dm家族史和高血压等混杂因素后,结果显示:与c等位基因相比,t等位基因人群患igr和t2dm的or值分别为0.907(0.783-1.050)和0.992(0.874-1.127)。与cc基因型相比,tt基因型人群患igr和t2dm的or值分别为0.828(0.618-1.109)和0.983(0.766-1.261)。ct+tt基因型人群患igr和t2dm的or值分别为0.917(0.723-1.164)和0.911(0.739-1.122)。结论:gckr基因rs780094位点的t等位基因可降低igr和t2dm的患病风险。t等位基因使igr和t2dm的患病风险分别降低了9.3%和0.8%。第三部分血浆尿酸水平与gckr基因交互作用与2型糖尿病的关联性目的:在前两部分研究的基础上,进一步分析女性血浆ua水平与gckr基因多态性之间的交互作用对t2dm患病风险的影响。方法:研究对象同第一部分。血浆ua检测见第一部分,gckr基因rs780094位点的基因分型见第二部分。结果:研究结果显示,在女性研究对象中,血浆ua水平(3.95-7.00mg/dl)与rs780094基因多态性与t2dm患病风险存在交互作用(pinteraction=0.031)。在校正年龄、性别、BMI、DM家族史和高血压后,CC和TT基因型背景下血浆UA浓度每升高1 mg/dL,患T2DM的OR值分别为5.523(2.665-11.447)和2.302(1.140-3.759),且均存在显著地线性剂量反应关系(P=0.001)。GCKR rs780094位点的CC基因型增强了血浆UA水平对T2DM的患病风险的影响;血浆UA浓度升高也增强了CC基因型对T2DM的危害作用。在男性研究对象中,血浆UA水平(≤6.00 mg/dL)与rs780094基因多态性之间与T2DM的患病风险之间不存在交互作用(Pinteraction0.05)。结论:研究结果显示,在女性研究对象中,血浆UA水平(3.95-7.00 mg/dL)与rs780094基因多态性与T2DM患病风险存在交互作用。CC基因型增强了血浆UA水平对T2DM的患病风险的影响;血浆UA浓度升高也增强了CC基因型对T2DM的危害作用。在男性研究对象中,血浆UA水平(≤6.00 mg/dL)与rs780094基因多态性之间与T2DM的患病风险之间不存在交互作用。
[Abstract]:Methods: The subjects were screened for diabetes mellitus by OGTT test. According to the diagnostic criteria recommended by WHO in 1999, the subjects were divided into normal control group, IGR group and T2DM group. Results: A total of 3 685 subjects were enrolled in this study, including 1 322 T2DM patients, 775 IGR patients and 1 588 normal controls, 59.91%, 63.10% and 58.06% males respectively. The plasma UA concentrations in the control group, IGR group and T2DM group were 4.69 (3.91-5.72) mg/dL, 5.09 (4.07-6.18) mg/dL and 5.22 (4.26-6) mg/dL, respectively. 6.27 mg/dL, compared with the control group, the plasma UA levels in IGR group and T2DM group were significantly higher (P 0.001). According to the distribution of uric acid in the control group, UA levels were divided into three groups. After adjusting for confounding factors such as age, sex, BMI, family history of DM and hypertension, the results showed that the risk of IGR and T2DM in the high UA level group was higher than that in the low UA level group. The correlation between plasma UA level and T2DM was stratified by sex and divided into four groups according to the distribution of plasma UA level. After adjusting for the above confounding factors, the correlation between plasma UA level and T2DM risk showed a U-shaped curve. The OR values of T2DM and IGR + T2DM were 2.614 (1.805-3.787) and 2.842 (2.022-3.993) respectively in the women with high uric acid quartile compared with those with low quartile. Conclusion: Plasma UA levels can significantly increase the risk of T2DM. The association between serum levels and risk of type 2 diabetes mellitus showed a U-shaped curve. The risk of type 2 diabetes mellitus was significantly increased in women with high uric acid levels (3.95-7.00 mg/dl) quartile compared with low quartile. Results: the frequencies of the minimal alleles (c alleles) at the gckrrs 780094 locus in the control group, IGR group and T2DM group were 48.7%, 49.0% and 51.3% respectively. After family history and hypertension, the OR values of IGR and T2DM were 0.907 (0.783-1.050) and 0.992 (0.874-1.127) respectively, compared with those of C allele. Compared with those of C C genotype, the OR values of t t genotype were 0.828 (0.618-1.109) and 0.983 (0.766-1.261) respectively. The or values of Gckr and T2DM were 0.917 (0.723-1.164) and 0.911 (0.739-1.122), respectively. Conclusion: The T allele at rs780094 of GCKR gene can reduce the risk of IGR and t2dm. The T allele reduced the risk of IGR and T2DM by 9.3% and 0.8% respectively. The third part was the association between plasma uric acid level and GCKR gene interaction and type 2 diabetes mellitus. AIM: To further analyze the effect of the interaction between plasma UA level and GCKR gene polymorphism on the risk of T2DM in women based on the previous two studies.METHODS: The subjects were the same as the first part. In female subjects, plasma UA levels (3.95-7.00mg/dl) interacted with rs780094 gene polymorphisms and T2DM risk (pinteraction = 0.031). For each 1 mg/dL increase in plasma UA levels in the context of CC and TT genotypes, the OR values for T2DM were 5.523 (2.665-11.447) and 2.302 (1.302) after adjusting for age, sex, BMI, DM family history, and hypertension. C genotypes at the GCKR rs780094 locus enhanced the effect of plasma UA levels on the risk of T2DM; elevated plasma UA concentrations also enhanced the risk of CCgenotype on T2DM. In male subjects, plasma UA levels (< 6.00 mg/dL) and rs780094 gene polymorphisms were found. There was no interaction between sex and the risk of T2DM (Pinteraction 0.05). CONCLUSION: In female subjects, plasma UA levels (3.95-7.00 mg/dL) and rs780094 gene polymorphisms interacted with the risk of T2DM. CC genotypes enhanced the effect of plasma UA levels on the risk of T2DM. Increased concentrations of CC also increased the risk of T2DM. In male subjects, there was no interaction between plasma UA levels (<6.00 mg/dL) and rs780094 gene polymorphism and the risk of T2DM.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.1
本文编号：2186432
[Abstract]:Methods: The subjects were screened for diabetes mellitus by OGTT test. According to the diagnostic criteria recommended by WHO in 1999, the subjects were divided into normal control group, IGR group and T2DM group. Results: A total of 3 685 subjects were enrolled in this study, including 1 322 T2DM patients, 775 IGR patients and 1 588 normal controls, 59.91%, 63.10% and 58.06% males respectively. The plasma UA concentrations in the control group, IGR group and T2DM group were 4.69 (3.91-5.72) mg/dL, 5.09 (4.07-6.18) mg/dL and 5.22 (4.26-6) mg/dL, respectively. 6.27 mg/dL, compared with the control group, the plasma UA levels in IGR group and T2DM group were significantly higher (P 0.001). According to the distribution of uric acid in the control group, UA levels were divided into three groups. After adjusting for confounding factors such as age, sex, BMI, family history of DM and hypertension, the results showed that the risk of IGR and T2DM in the high UA level group was higher than that in the low UA level group. The correlation between plasma UA level and T2DM was stratified by sex and divided into four groups according to the distribution of plasma UA level. After adjusting for the above confounding factors, the correlation between plasma UA level and T2DM risk showed a U-shaped curve. The OR values of T2DM and IGR + T2DM were 2.614 (1.805-3.787) and 2.842 (2.022-3.993) respectively in the women with high uric acid quartile compared with those with low quartile. Conclusion: Plasma UA levels can significantly increase the risk of T2DM. The association between serum levels and risk of type 2 diabetes mellitus showed a U-shaped curve. The risk of type 2 diabetes mellitus was significantly increased in women with high uric acid levels (3.95-7.00 mg/dl) quartile compared with low quartile. Results: the frequencies of the minimal alleles (c alleles) at the gckrrs 780094 locus in the control group, IGR group and T2DM group were 48.7%, 49.0% and 51.3% respectively. After family history and hypertension, the OR values of IGR and T2DM were 0.907 (0.783-1.050) and 0.992 (0.874-1.127) respectively, compared with those of C allele. Compared with those of C C genotype, the OR values of t t genotype were 0.828 (0.618-1.109) and 0.983 (0.766-1.261) respectively. The or values of Gckr and T2DM were 0.917 (0.723-1.164) and 0.911 (0.739-1.122), respectively. Conclusion: The T allele at rs780094 of GCKR gene can reduce the risk of IGR and t2dm. The T allele reduced the risk of IGR and T2DM by 9.3% and 0.8% respectively. The third part was the association between plasma uric acid level and GCKR gene interaction and type 2 diabetes mellitus. AIM: To further analyze the effect of the interaction between plasma UA level and GCKR gene polymorphism on the risk of T2DM in women based on the previous two studies.METHODS: The subjects were the same as the first part. In female subjects, plasma UA levels (3.95-7.00mg/dl) interacted with rs780094 gene polymorphisms and T2DM risk (pinteraction = 0.031). For each 1 mg/dL increase in plasma UA levels in the context of CC and TT genotypes, the OR values for T2DM were 5.523 (2.665-11.447) and 2.302 (1.302) after adjusting for age, sex, BMI, DM family history, and hypertension. C genotypes at the GCKR rs780094 locus enhanced the effect of plasma UA levels on the risk of T2DM; elevated plasma UA concentrations also enhanced the risk of CCgenotype on T2DM. In male subjects, plasma UA levels (< 6.00 mg/dL) and rs780094 gene polymorphisms were found. There was no interaction between sex and the risk of T2DM (Pinteraction 0.05). CONCLUSION: In female subjects, plasma UA levels (3.95-7.00 mg/dL) and rs780094 gene polymorphisms interacted with the risk of T2DM. CC genotypes enhanced the effect of plasma UA levels on the risk of T2DM. Increased concentrations of CC also increased the risk of T2DM. In male subjects, there was no interaction between plasma UA levels (<6.00 mg/dL) and rs780094 gene polymorphism and the risk of T2DM.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.1
【参考文献】
相关硕士学位论文 前1条
1 孙琳;高尿酸血症在2型糖尿病发生中的作用分析[D];吉林大学;2013年
，本文编号：2186432
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