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脂蛋白脂肪酶基因多态性与血糖水平、胰岛素抵抗的相关性研究
A study on the association of lipoprotein lipase gene polymorphisms with glucose level and insulin resistance
【Author】 Liu Na;Ren Lu-ping;Chen Shu-chun;Department of Endocrinology,Hebei General Hospital;
【机构】 河北省人民医院内分泌一科;
【摘要】 目的:研究表明LPL基因是2型糖尿病的重要候选基因,尤其是位于LPL基因内显子8中的HindⅢ酶切位点突变能够改变LPL活性,是影响血浆TG,FFA及HDL水平的重要因素,与高脂血症、冠心病与动脉粥样硬化的发病密切相关。本研究以高糖人群为研究对象,探讨HindⅢ酶切位点突变与糖代谢紊乱、胰岛素抵抗的关系。方法:在健康查体人群中按照空腹血糖水平选取高糖组232人(血糖≥6.1mmol/L)和对照组109人(血糖≤6.0mmol/L),两组人群分别测定空腹胆固醇(TC)、甘油三酯(TG)、空腹胰岛素(FINS)及游离脂肪酸(FFA)水平;采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析LPL基因HindⅢ多态性。高糖组和对照组间统计指标的比较采用t检验;高糖组和对照组间基因型频率和等位基因频率分布的差异用x2检验;在不同基因型中各个临床参数比较采用方差分析;并通过Logistic回归分析高血糖的影响因素。结果:根据LPL第8内含子有无HindⅢ酶切位点,分为H+H+、H+H-、H-H-三种基因型和H+、H-两种等位基因。①在高糖组中H+等位基因和H+H+基因型分布频率分别高于对照组(P<0.05),差异有统计学意义;②高糖组中合并高TG血症组的H+等位基因频率和H+H+基因型分布频率分别高于正常TG组,差异有统计学意义(P<0.05);而对照组中,合并高TG血症组的H+等位基因频率和H+H+基因型分布频率分别高于正常TG组,但无统计学意义(P>0.05);③在所有样本中,H+H+基因型组BMI、WC、TG、FFA、FINS、空腹血糖和HOMA-IR均高于其他组,差异有统计学意义(P<0.05);④通过Logistic回归提示高血糖的独立危险因素是腰围、FFA和HOMA-IR。(1)LPL基因3种基因型H+H+、H+H-和H-H-,它们在高糖组和对照组的分布频率分别为:H+H+0.647和0.569;H+H-0.319和0.33;H-H-0.034和0.101。含HindⅢ酶切位点的"H+"等位基因在高糖组和对照组的分布频率分别为0.806和0.734,无HindⅢ酶切位点的"H-"等位基因在高糖组和对照组的分布频率分别为0.194和0.266。在高糖组"H+"等位基因和H+H+基因型分布频率分别高于对照组(P<0.05),差异有统计学意义。结论:脂蛋白脂酶基因HindⅢ酶切位点多态性与TG升高密切相关,与血糖升高无明显关联,血糖升高与腰围、FFA和HOMA-IR有独立相关性。
【Abstract】 Objective:To explore the relationship between gene polymorphism of HindⅢ at intron 8 in lipoprotein lipase and glucose metabolism dysfunction.Methods:The study population consisted of 232 patients with high blood glucose and 109 control subjects according to fasting blood glucose level.Total cholesterol、triacylglycerol、fasting insulin and free fatty acid were detected.PCR-RFLP methods were used to determine the DNA polymorphism of 8th intron at LPL gene.Results:①There was significant difference in frequencies of genotypes and alleles between the two groups.②In high blood glucose group,the H+H+ genotype frequency and the H+ allelic frequency of the hyertriglyceridemia group were significantly higher than those of normal triglycerides control group.③Higher levels of WC、BMI、TG、FFA、FINS、FBG and HOMA-IR(P <0.05) were observed in samples with H+H+ genotype than in samples with(H+H-and H-H-)genotypes.④Logistic regressive analysis showed that the risk factors of high blood glucose are WC,FFA and HOMA-IR.Conclusion:The LPL-Hind Ⅲ genotype polymorphisms is not separately associated with high blood glucose.Both WC,FFA and HOMA—IR are separately correlated with high blood glucose.
【Key words】 Type 2 diabetes mellitus; Insulin resistance; lipoprotein lipase gene; Restriction fragment length polymorphism;
- 【会议录名称】 2008中国医师协会内分泌代谢科医师分会年会论文汇编
- 【会议名称】2008中国医师协会内分泌代谢科医师分会年会
- 【会议时间】2008-09-18
- 【会议地点】中国北京
- 【分类号】R587.1
- 【主办单位】中国医师协会内分泌代谢科医师分会