2型糖尿病患者脂蛋白酯酶基因多态性与血甘油三酯水平的关系

目的 探讨2型糖尿病患者脂蛋白酯酶（LPL）常见基因多态性与血甘油三酯水平的关系.方法选取2008年6月至2010年4月郑州大学第一附属医院内分泌科初次住院的152例2型糖尿病患者为病例组,入选患者均符合1999年WHO诊断标准,以年龄、地区、性别频数匹配从河南省级医院体检人群中抽取145名健康体检者为对照组,对两组分别抽血提取DNA,PCR扩增LPL基因特定片段,限制性内切酶TaqⅠ、RsaⅠ和HinfⅠ、PvuⅡ进行酶切反应,分析酶切产物.聚丙烯酰胺凝胶电泳,分析电泳结果,所有患者均测定血甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A（ApoA）、载脂蛋白B（ApoB）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、胰岛素抵抗指数（HOMA-IR）.统计学方法采用χ^2检验检测观察到的基因型是否符合遗传学平衡定律,组间血脂水平比较采用t检验,基因型频率和等位基因频率的差异比较用χ^2检验,以α=0.05作为检验水准.结果 LPL基因Ser447Ter位点中病例组G等位基因和CG基因型频率均低于对照组（3.3% vs 12.4%;6.6% vs 24.8%）,差异均有统计学意义（均P〈0.05）;病例组和对照组CG基因型携带者血TG水平均低于非携带者（分别为1.39±0.11 vs 1.68±0.18;1.24±0.08 vs 1.48±0.15;P〈0.05）,差异有统计学意义.对照组的CG基因型HDL-C高于CC基因型（1.46±0.06 vs 1.35±0.08;P〈0.05）,差异有统计学意义.病例组和对照组中均未发现Asp9Asn及Asn291Ser,两组间PvuⅡ酶切基因型出现频率差异无统计学意义.各组基因频率符合Hardy-Weinberg平衡定律吻合度检验.结论 我国河南汉族人群脂蛋白酯酶基因Asp9Asn、Asn291Ser、PvuⅡ酶切位点多态性与2型糖尿病无明显关联,而Ser447Ter多态性可以降低血TG水平,对于降低2型糖尿病发病而言可能是一个保护性突变.

Association of lipoprotein lipase gene polymorphism and blood triglyceride in patients with type 2 diabetes mellitus

Objective To investigate the association between the polymorphisms of the LPL gene and blood triglyceride in type 2 diabetes mellitus(DM). Methods 152 first admission patients with Type 2 DM were chosen from the first affiliated hospital of Zhengzhou University and 145 control subjects were observed. Blood DNA samples were obtained from subjects in both groups,PCR amplification were performed on particular LPL gene fragments,restriction enzyme digestion and their products analyzed.All patients were measured TC,TG,HDL-C,LDL-C,ApoA.ApoB,FBG,HbA1c,HOMA-IR. Detected by statistical methods χ2 test whether the observed genetic equilibrium genotype. T check was used to compare the intergroup blood fat levels, the disparation of genotypic frequency and allele frequency were compared with χ2 test with the test criterion α=0.05. Results LPL gene locus in the case group, Ser447Ter G allele and CG genotypes were lower than that of control group(3.3% vs 12.4%;6.6% vs 24.8%)and there was statistical significance for all differences(all P<0.05). Both in case group and control group, CG genotype carriers′ plasma TG levels were lower than that of non-carrier (respectively: 1.39±0.11 vs 1.68±0.18;1.24±0.08 vs 1.48±0.15), and the differences have statistical significance (P<0.05). Control groups′ CG genotype HDL-C were higher than CC genotype (1.46±0.06 vs 1.35±0.08;P<0.05 ). Asp9Asn and Asn291Ser variants were not found either in T2DM patients or in controls. There were no significant differences in the frequencies of LPL PvuⅡmutations either. And both groups′ gene frequencies were precisely in line with the balance law Hardy-Weinberg detection. Conclusions Asp9Asn,Asn291Ser and PvuⅡpolymorphisms in the LPL gene bear no relationship with the type 2 diabetes mellitus in Han people in Henan province. However, the Ser447Ter polymorphism in the LPL gene may reduce plasma triglyceride level, which maybe a protective mutation in reduction of the incidence of type 2 diabetes mellitus.