【摘要】：目的 探討ADP-核糖基化樣因子15(ADP-ribosylation factor-like 15,ARL15)和脂聯(lián)素兩個基因的3個單核苷酸多態(tài)性(SNPs)聯(lián)合作用與延邊朝鮮族2型糖尿病(type 2 diabetes mellitus,T2DM)的關(guān)系。方法采用病例對照設(shè)計,隨機選擇144例T2DM患者以及葡萄糖耐量正常(NGT)對照人群140例,使用單堿基延伸方法檢測ARL15基因的rs26770(A/G)和脂聯(lián)素基因的rs1501299(C/A)及rs2241766(T/G)的基因型；采用酶聯(lián)免疫吸附試驗(enzyme linked immunosorbent assay, ELISA)法檢測空腹血漿的ARL15(PARL15)、脂聯(lián)素(PA)和胰島素(INS)水平,同時檢測生理生化指標[體重、身高、腰臀比、空腹血糖(FPG),總膽固醇(TC)、甘油三酯(TG)、高密度脂蛋白膽固醇(HDL-C)、低密度脂蛋白膽固醇(LDL-C)]。結(jié)果1.3個SNPs等位基因頻率、基因型頻率在NGT組、T2DM組之間均符合Hardy-Weinberg平衡定律(P0.05),但未發(fā)現(xiàn)T2DM組與NGT組之間等位基因頻率和基因型頻率存在顯著性差異(P0.05)。2.聯(lián)合基因型分析發(fā)現(xiàn)(rs26770、rs1501299和rs2241766)GG-AA-TT聯(lián)合基因型在T2DM組頻率(5.6%)明顯高于NGT組(0.0%),兩組差異具有統(tǒng)計學(xué)意義(P0.05)。3.T2DM患者的PA含量顯著低于NGT組,而PARL15含量顯著高于NGT組,差異有統(tǒng)計學(xué)意義(P0.05)。4.3個SNP的基因型與臨床指標關(guān)聯(lián)分析結(jié)果首次發(fā)現(xiàn)：延邊朝鮮族NGT組內(nèi)脂聯(lián)素基因rs2241766-TT基因型者PA水平顯著低于GG+GT基因型,而TG水平顯著高于GG+GT基因型(P0.05),呈現(xiàn)顯性遺傳模式；而ARL15基因rs26770-GG基因型者HDL-C低于AA+AG基因型者(P0.05),在T2DM組內(nèi)ARL15基因rs26770-GG基因型者BMI低于AA+AG基因型者(P0.05),而PA高于AA+AG者(P0.05),呈隱性遺傳模式。5.中國延邊朝鮮族3個SNPs的等位基因頻率與HapMap數(shù)據(jù)庫比較發(fā)現(xiàn)rs26770等位基因G頻率顯著低于歐洲人(CEU)(P0.01),與中國北京漢族人(CHB)、日本東京人(JPT)和尼日利亞伊巴丹的約魯巴人(YRI)差異無統(tǒng)計學(xué)意義(P0.05);rs1501299-A等位基因頻率低于YRI(P0.05),與CHB、JPT和YRI差異無統(tǒng)計學(xué)意義(P0.05)；rs2241766等位基因G頻率顯著高于CEU和YRI(P0.01),與CHB、JPT差異無統(tǒng)計學(xué)意義(P0.05)。結(jié)論1.ARL15和脂聯(lián)素基因3個SNPs (rs26770,rs1501299,rs2241766)的聯(lián)合基因型GG-AA-TT可能是延邊朝鮮族T2DM的危險基因型組合；2.脂聯(lián)素基因rs2241766-G上調(diào)PA水平,下調(diào)TG水平；3.高PARL15血癥與T2DM發(fā)生高度相關(guān)；4.ARL15基因和脂聯(lián)素基因的SNPs(rs26770, rs1501299,rs2241766)等位基因頻率存在種族差異。
[Abstract]:Aim to investigate the relationship between the combination of three single nucleotide polymorphisms (SNPs) of ADP- ribonucleotide like factor 15 (ADP-ribosylation factor-like 15, ARL15) and adiponectin gene and type 2 diabetes mellitus,T2DM in Yanbian Korean nationality. Methods A case-control design was used to randomly select 144 patients with T2DM and 140 controls with normal glucose tolerance (NGT). Single base extension method was used to detect the genotypes of rs26770 (A? G) of ARL15 gene, rs1501299 (C) and rs2241766 (T? G) of adiponectin gene. The levels of ARL15 (PARL15), adiponectin (PA) and insulin (INS) in fasting plasma were measured by enzyme linked immunosorbent assay (enzyme linked immunosorbent assay, ELISA), and the physiological and biochemical indexes (weight, height, waist hip ratio, fasting blood glucose (FPG),) were also measured. Total cholesterol, (TC), triglyceride, (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, low density lipoprotein cholesterol (LDL-C). Results 1.3allele frequencies and genotype frequencies of SNPs were in accordance with Hardy-Weinberg equilibrium law between NGT group and T2DM group (P0.05). However, no significant difference was found in allele frequency and genotype frequency between T2DM group and NGT group (P0.05). The combined genotype analysis (rs26770,rs1501299 and rs2241766) showed that the frequency of GG-AA-TT co-genotype in T2DM group (5.6%) was significantly higher than that in NGT group (0.0%). 3. The content of PA in T2 DM patients was significantly lower than that in NGT group, while the PARL15 content was significantly higher than that in NGT group. The results of association analysis between SNP genotypes and clinical indexes showed for the first time that the PA level of rs2241766-TT genotype of adiponectin gene in Yanbian Korean group was significantly lower than that of GG GT genotype, which was significantly lower than that of adiponectin gene rs2241766-TT genotype in Yanbian Korean nationality. The level of TG was significantly higher than that of GG GT genotype (P0.05), showing a dominant genetic model. The HDL-C of rs26770-GG genotype of ARL15 gene was lower than that of AA AG genotype (P0.05), and the BMI of rs26770-GG genotype of ARL15 gene was lower than that of AA AG genotype in T2DM group (P0.05), while PA was higher than that of AA AG (P0.05), and that of rs26770-GG genotype of ARL15 gene was lower than that of AA AG genotype (P0.05). Recessive inheritance pattern. 5. Compared with HapMap database, the allele frequencies of three SNPs alleles in Korean population in Yanbian, China, were significantly lower than those in European (CEU) (P0.01), and were significantly lower than those of (CHB), in Chinese Han nationality in Beijing (P0.01). There was no significant difference in (YRI) between (JPT) from Tokyo, Japan and Yoruba from Ibadan, Nigeria (P0.05). The allele frequency of rs1501299-A was lower than that of YRI (P0.05), and there was no significant difference with CHB,JPT and YRI (P0.05). The G frequency of rs2241766 allele was significantly higher than that of CEU and YRI (P0.01), but had no significant difference with CHB,JPT (P0.05). Conclusion the combined genotype GG-AA-TT of 1.ARL15 and adiponectin gene three SNPs (rs26770,rs1501299,rs2241766) may be a risk genotype combination of T2DM in Yanbian Korean nationality. Adiponectin gene rs2241766-G up-regulated the level of PA and down-regulated the level of TG; The frequency of SNPs (rs26770, rs1501299,rs2241766) allele of 4.ARL15 gene and adiponectin gene was significantly different between 4.ARL15 gene and adiponectin 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】：2015
【分類號】：R587.1

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