SAA1水平及其基因rs12218多態(tài)性與2型糖尿病及糖尿病腎病的相關(guān)性研究
發(fā)布時(shí)間：2018-07-14 08:07
【摘要】：目的：探討血清淀粉樣蛋白Al(serum amyloid Al,SAA1)水平及其rs12218基因多態(tài)性與2型糖尿病(T2DM)及糖尿病腎病(DN)的相關(guān)性。 研究方法：選取延邊地區(qū)正常對照組(normal glucose tolerant, NGT)50例,T2DM組215例。T2DM組再根據(jù)尿蛋白排泄率(UAER)進(jìn)一步分為糖尿病無腎病組(NDN組)65例,糖尿病腎病組(DN組)140例。采用酶聯(lián)免疫法(ELISA)測定樣本血清的SAA1水平。用熒光測序法測定基因序列,將基因組DNA進(jìn)行擴(kuò)增、純化后進(jìn)行DNA測序,S anger雙脫氧鏈終止法基因分型。采用放射免疫法測定尿液中白蛋白的濃度。用SPSS17.0統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)的統(tǒng)計(jì)分析。計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,組間比較行單因素方差分析。采用Spearman相關(guān)分析對SAA1與臨床各生化指標(biāo)進(jìn)行相關(guān)分析。組間基因型及等位基因頻率比較采用Pearson's χ2檢驗(yàn)。采用Logistic回歸分析篩選DN病變的危險(xiǎn)因素。 結(jié)果：1.NDN組SAA1水平高于DN組,并且DN組SAA1水平高于NDN組,有統(tǒng)計(jì)學(xué)差異(P0.05)。 2.NDN組和DN組的SBP、DBP、FPG、2hPG、HbA1c、CREA指數(shù)高于NGT組,有統(tǒng)計(jì)學(xué)差異(P0.05)。且DN組的SBP、DBP、FPG、2hPG、HbAlc、CREA指數(shù)高于NDN組,有統(tǒng)計(jì)學(xué)差異(P0.05)。 3.SAA1與年齡、病程、FPG、2hPG、HbAlc、CREA呈明顯正相關(guān),有統(tǒng)計(jì)學(xué)差異(P0.05)。 4.延邊朝鮮族、漢族人群的SAA1基因rs12218的等位基因頻率分布與HapMap數(shù)據(jù)庫(SS40072010)的歐洲人(CEU)、中國北京漢族人(HCB)、日本東京人(JPT)和非洲約魯巴人(YRI)進(jìn)行比較,結(jié)果顯示：延邊朝鮮族和漢族人群的rs12218(A)位點(diǎn)等位基因頻率無民族差異(p0.05),延邊朝鮮族rs12218-A等位基因頻率顯著高于CEU (p0.01)。與HCB、JPT無統(tǒng)計(jì)學(xué)差異。在延邊漢族rs12218-A等位基因頻率與CEU、HCB、JPT比較,均無統(tǒng)計(jì)學(xué)差異(p0.05) 5.rs12218-G等位基因頻率在NDN組中出現(xiàn)的頻率高于NGT組(32.3%16.0%,P=0.045),并且rs12218-G等位基因頻率在DN組中出現(xiàn)的頻率高于NDN組(33.2%32.3%,P=0.046)。在顯性模型(AG+GG:AA)分析中,攜帶AG+GG基因型患NDN的風(fēng)險(xiǎn)是NGT組的1.673倍(P=0.04, OR=1.673,95%CI:0.76-3.69),'并且在顯性模型(AG+GG:AA)分析中,攜帶AG+GG基因型患DN的風(fēng)險(xiǎn)是NDN1.46倍(P=0.046, OR=1.673,95%CI:0.67-3.35) 6.NGT組、NDN組、DN組各組內(nèi)AG+GG基因型者SAA1水平明顯高于AA基因型者SAA1水平,均有統(tǒng)計(jì)學(xué)差異(P0.05)。 7.rs12218多態(tài)基因型在NGT、NDN、DN各組內(nèi)臨床指標(biāo)未發(fā)現(xiàn)存在顯著性差異(P0.05);rs12218多態(tài)基因型的顯性模式在NGI、NDN、DN各組內(nèi)臨床指標(biāo)未發(fā)現(xiàn)存在顯著性差異(P0.05)；rs12218多態(tài)基因型的隱性模式在NGT、NDN、DN各組內(nèi)臨床指標(biāo)未發(fā)現(xiàn)存在顯著性差異(P0.05)。 8.PBG、SAA1水平、AG+GG基因型為DN的危險(xiǎn)因素。 結(jié)論： 1.SAA1水平與T2DM及DN呈正相關(guān)。 2.SAA1基因rs12218-G等位基因可能是DN的易感基因。 3.SAA1基因rs12218位點(diǎn)存在種族差異。
[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 鹵standard deviation (x 鹵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.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R587.2;R692
本文編號：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 鹵standard deviation (x 鹵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.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R587.2;R692
【參考文獻(xiàn)】
相關(guān)期刊論文 前6條
1 劉鋼,王蘭蘭,李立新,武永康,王玲,王忠明,謝其冰;血清淀粉樣蛋白A——類風(fēng)濕關(guān)節(jié)炎的一個(gè)炎性指標(biāo)[J];中華風(fēng)濕病學(xué)雜志;2002年02期
2 胡善聯(lián);劉國恩;許樟榮;李大魁;胡永華;;我國糖尿病流行病學(xué)和疾病經(jīng)濟(jì)負(fù)擔(dān)研究現(xiàn)狀[J];中國衛(wèi)生經(jīng)濟(jì);2008年08期
3 朱華;王娟;林燕;張們;劉家民;;血清淀粉樣蛋白A的研究進(jìn)展[J];心血管病學(xué)進(jìn)展;2007年01期
4 蘇愛梅;老年代謝綜合征血漿游離脂肪酸、氧化低密度脂蛋白的變化和臨床意義[J];江蘇醫(yī)藥;2005年05期
5 龔大為;李平;朱大龍;;脂肪細(xì)胞因子研究進(jìn)展[J];中國糖尿病雜志;2007年10期
6 盛秀芝;蔡溢;王濤;;血清淀粉樣蛋白A在糖尿病腎病早期診斷中的價(jià)值[J];中國實(shí)驗(yàn)診斷學(xué);2010年05期
，本文編號：2121013
本文鏈接：http://sikaile.net/yixuelunwen/mjlw/2121013.html
最近更新
教材專著
