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延边朝鲜族ARL15和脂联素两个基因联合作用与2型糖尿病相关性研究

发布时间:2019-03-29 06:20
【摘要】:目的 探讨ADP-核糖基化样因子15(ADP-ribosylation factor-like 15,ARL15)和脂联素两个基因的3个单核苷酸多态性(SNPs)联合作用与延边朝鲜族2型糖尿病(type 2 diabetes mellitus,T2DM)的关系。方法采用病例对照设计,随机选择144例T2DM患者以及葡萄糖耐量正常(NGT)对照人群140例,使用单碱基延伸方法检测ARL15基因的rs26770(A/G)和脂联素基因的rs1501299(C/A)及rs2241766(T/G)的基因型;采用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)法检测空腹血浆的ARL15(PARL15)、脂联素(PA)和胰岛素(INS)水平,同时检测生理生化指标[体重、身高、腰臀比、空腹血糖(FPG),总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]。结果1.3个SNPs等位基因频率、基因型频率在NGT组、T2DM组之间均符合Hardy-Weinberg平衡定律(P0.05),但未发现T2DM组与NGT组之间等位基因频率和基因型频率存在显著性差异(P0.05)。2.联合基因型分析发现(rs26770、rs1501299和rs2241766)GG-AA-TT联合基因型在T2DM组频率(5.6%)明显高于NGT组(0.0%),两组差异具有统计学意义(P0.05)。3.T2DM患者的PA含量显著低于NGT组,而PARL15含量显著高于NGT组,差异有统计学意义(P0.05)。4.3个SNP的基因型与临床指标关联分析结果首次发现:延边朝鲜族NGT组内脂联素基因rs2241766-TT基因型者PA水平显著低于GG+GT基因型,而TG水平显著高于GG+GT基因型(P0.05),呈现显性遗传模式;而ARL15基因rs26770-GG基因型者HDL-C低于AA+AG基因型者(P0.05),在T2DM组内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),呈隐性遗传模式。5.中国延边朝鲜族3个SNPs的等位基因频率与HapMap数据库比较发现rs26770等位基因G频率显著低于欧洲人(CEU)(P0.01),与中国北京汉族人(CHB)、日本东京人(JPT)和尼日利亚伊巴丹的约鲁巴人(YRI)差异无统计学意义(P0.05);rs1501299-A等位基因频率低于YRI(P0.05),与CHB、JPT和YRI差异无统计学意义(P0.05);rs2241766等位基因G频率显著高于CEU和YRI(P0.01),与CHB、JPT差异无统计学意义(P0.05)。结论1.ARL15和脂联素基因3个SNPs (rs26770,rs1501299,rs2241766)的联合基因型GG-AA-TT可能是延边朝鲜族T2DM的危险基因型组合;2.脂联素基因rs2241766-G上调PA水平,下调TG水平;3.高PARL15血症与T2DM发生高度相关;4.ARL15基因和脂联素基因的SNPs(rs26770, rs1501299,rs2241766)等位基因频率存在种族差异。
[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.
【学位授予单位】:延边大学
【学位级别】:硕士
【学位授予年份】:2015
【分类号】:R587.1

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