【摘要】：第一部分血漿尿酸水平與2型糖尿病的關(guān)聯(lián)性目的:探討血漿UA水平與T2DM的關(guān)聯(lián)性。方法:研究對(duì)象為利用OGTT試驗(yàn)進(jìn)行糖尿病篩檢的人群。根據(jù)WHO 1999年推薦的診斷標(biāo)準(zhǔn),將研究對(duì)象分為正常對(duì)照組、IGR和T2DM組。利用全自動(dòng)生化分析儀(尿酸酶-過氧化物酶法)檢測(cè)血漿UA的濃度。結(jié)果:本研究共納入3685名研究對(duì)象,其中T2DM病例1322名,IGR病例775名,正常對(duì)照1588名;男性分別占59.91%、63.10%和58.06%。對(duì)照組、IGR組和T2DM組血漿UA的濃度分別為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,與對(duì)照組相比IGR組和T2DM組的血漿UA濃度顯著升高(P0.001)。按照對(duì)照組尿酸的分布,將血漿UA水平分為三組,校正年齡、性別、BMI、DM家族史和高血壓等混雜因素后結(jié)果顯示:血漿UA水平高濃度組的與低濃度組相比IGR和T2DM的患病風(fēng)險(xiǎn)分別增加了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)。對(duì)血漿UA水平與T2DM的關(guān)聯(lián)按性別進(jìn)行分層分析,按血漿UA水平的分布分別分為四分位組:校正以上混雜因素后,血漿UA水平與T2DM患病風(fēng)險(xiǎn)之間的關(guān)聯(lián)呈現(xiàn)U型曲線的趨勢(shì)。隨尿酸水平的升高,T2DM的患病風(fēng)險(xiǎn)呈現(xiàn)先降低后升高。女性尿酸水平高四分位組的與低四分位相比,患T2DM和IGR+T2DM的OR值分別為2.614(1.805-3.787)和2.842(2.022-3.993)。結(jié)論:血漿UA水平可顯著增加T2DM的患病風(fēng)險(xiǎn)。在性別分層分析中,血漿ua水平與t2dm患病風(fēng)險(xiǎn)之間的關(guān)聯(lián)呈現(xiàn)u型曲線的趨勢(shì)。女性尿酸水平(3.95-7.00mg/dl)高四分位組與低四分位組相比可顯著增加t2dm的患病風(fēng)險(xiǎn)。第二部分gckr基因多態(tài)性與2型糖尿病的關(guān)聯(lián)性目的:探討gckr基因rs780094位點(diǎn)基因多態(tài)性與t2dm和igr患病風(fēng)險(xiǎn)的關(guān)聯(lián)性。方法:研究對(duì)象同第一部分。采用taqman探針熒光定量pcr法,對(duì)gckr基因rs780094位點(diǎn)進(jìn)行基因分型。結(jié)果:對(duì)照組、igr組和t2dm組人群gckrrs780094位點(diǎn)的最小等位基因(c等位基因)頻率分別為:48.7%、49.0%和51.3%。校正年齡、性別、bmi、dm家族史和高血壓等混雜因素后,結(jié)果顯示:與c等位基因相比,t等位基因人群患igr和t2dm的or值分別為0.907(0.783-1.050)和0.992(0.874-1.127)。與cc基因型相比,tt基因型人群患igr和t2dm的or值分別為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值分別為0.917(0.723-1.164)和0.911(0.739-1.122)。結(jié)論:gckr基因rs780094位點(diǎn)的t等位基因可降低igr和t2dm的患病風(fēng)險(xiǎn)。t等位基因使igr和t2dm的患病風(fēng)險(xiǎn)分別降低了9.3%和0.8%。第三部分血漿尿酸水平與gckr基因交互作用與2型糖尿病的關(guān)聯(lián)性目的:在前兩部分研究的基礎(chǔ)上,進(jìn)一步分析女性血漿ua水平與gckr基因多態(tài)性之間的交互作用對(duì)t2dm患病風(fēng)險(xiǎn)的影響。方法:研究對(duì)象同第一部分。血漿ua檢測(cè)見第一部分,gckr基因rs780094位點(diǎn)的基因分型見第二部分。結(jié)果:研究結(jié)果顯示,在女性研究對(duì)象中,血漿ua水平(3.95-7.00mg/dl)與rs780094基因多態(tài)性與t2dm患病風(fēng)險(xiǎn)存在交互作用(pinteraction=0.031)。在校正年齡、性別、BMI、DM家族史和高血壓后,CC和TT基因型背景下血漿UA濃度每升高1 mg/dL,患T2DM的OR值分別為5.523(2.665-11.447)和2.302(1.140-3.759),且均存在顯著地線性劑量反應(yīng)關(guān)系(P=0.001)。GCKR rs780094位點(diǎn)的CC基因型增強(qiáng)了血漿UA水平對(duì)T2DM的患病風(fēng)險(xiǎn)的影響;血漿UA濃度升高也增強(qiáng)了CC基因型對(duì)T2DM的危害作用。在男性研究對(duì)象中,血漿UA水平(≤6.00 mg/dL)與rs780094基因多態(tài)性之間與T2DM的患病風(fēng)險(xiǎn)之間不存在交互作用(Pinteraction0.05)。結(jié)論:研究結(jié)果顯示,在女性研究對(duì)象中,血漿UA水平(3.95-7.00 mg/dL)與rs780094基因多態(tài)性與T2DM患病風(fēng)險(xiǎn)存在交互作用。CC基因型增強(qiáng)了血漿UA水平對(duì)T2DM的患病風(fēng)險(xiǎn)的影響;血漿UA濃度升高也增強(qiáng)了CC基因型對(duì)T2DM的危害作用。在男性研究對(duì)象中,血漿UA水平(≤6.00 mg/dL)與rs780094基因多態(tài)性之間與T2DM的患病風(fēng)險(xiǎn)之間不存在交互作用。
[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.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R587.1

【參考文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 孫琳;高尿酸血癥在2型糖尿病發(fā)生中的作用分析[D];吉林大學(xué);2013年

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本文編號(hào)：2186432