中国汉族TRB3基因Q84R多态性与2型糖尿病相关性研究
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摘要
目的:研究中国汉族TRB3基因Q84R多态性与2型糖尿病的关系。
方法:随机选取汉族2型糖尿病患者106例,均来自甘肃省人民医院内分泌科住院部。汉族正常对照130例,来自甘肃省人民医院健康体检中心健康体检者,排除糖尿病,且无糖尿病家族史。用酚/氯仿法提取外周血基因组DNA,聚合酶链式反应(PCR)扩增目的DNA。采用连接酶检测反应(LDR)检测TRB3基因Q84R多态性。同时测量身高、体重、腰围、臀围,用全自动生化分析仪测定血浆总胆固醇、甘油三脂、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、空腹血糖,糖化血红蛋白分析仪测定HbA1c,放射免疫法测定空腹胰岛素;用公式计算HOMA胰岛素抵抗指数(HOMA-IR=FPG×FINS/22.5);用胰岛素敏感指数(ISI=1/FPG×FINS)来评价胰岛素敏感性;采用微软办公软件Excel 2003建立数据库,SPSS13.0软件进行统计学分析。
结果:(1)TRB3基因Q84R位点QQ、QR和RR三种基因型频率在正常对照组和2型糖尿病组分别为0.662、0.689;0.308、0.292和0.031、0.019;两组间QQ、QR与RR三种基因型频率进行比较,差异无统计意义(P＞0.05);(2)等位基因Q、R频率在正常对照组和2型糖尿病组分别为0.815、0.185和0.835、0.165,两组间比较差异无统计意义(P＞0.05);(3)正常对照组不同基因型间各临床特征之间的比较,R84基因型受试者的FINS、HOMA-IR和TG水平明显高于QQ基因型受试者,R84基因型的受试者LnISI水平明显低于QQ基因型受试者,且差异均有统计意义(P＜0.05);(4)2型糖尿病组不同基因型间各临床特征之间的比较,R84基因型受试者的FINS、HOMA-IR和TG水平明显高于QQ基因型受试者,R84基因型的受试者LnISI和TC水平明显低于QQ基因型受试者,且差异均有统计意义(P＜0.05)。
结论:(1)中国汉族存在TRB3基因Q84R位点多态性;(2)TRB3基因Q84R位点多态性与中国汉族2型糖尿病的发生无关;(3)TRB3基因Q84R位点多态性与中国汉族糖尿病和非糖尿病人群的空腹胰岛素水平和胰岛素抵抗相关;(4)TRB3基因Q84R位点多态性与中国汉族糖尿病和非糖尿病人群的甘油三酯水平相关,与糖尿病患者的总胆固醇水平相关。
Objectives: To investigate the association of TRB3 gene Q84R polymorphism with type 2 diabetes mellitus in Chinese Han population.
Methods: 106 type 2 diabetes patients were selected at random from our ward in Gansu Provincial People's Hospital. The control group was consisted of 130 subjects from Medical Examination Center (MEC) of Gansu Provincial People's Hospital, without diabetes mellitus and family history of diabetes. Total Genomic DNA from peripheral blood was extracted by Phenol/chloroform method. Target DNA was amplified by the Polymerase Chain Reaction (PCR) and the SNP Q84R in TRB3 gene was detected by ligase detection reaction (LDR). At the same time, we measured the body height, body weight, waist circumference, hip circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP). Total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and fasting blood glucose levels were determined by automatic biochemistry analyzer. Glycosylated hemoglobin (HbA1c) value was determined by HbA1c analyzer. Fasting insulin concentration was measured using insulin radioimmunoassay kit. The homeostasis model assessment insulin resistance index (HOMA-IR) was calculated by the formula: (fasting glucose [millimoles per liter]×fasting insulin [microunits per milliliter])/22.5. ISI (insulin sensitivity index), 1/FPG×FINS, was used to assess Insulin sensitivity. And Microsoft Office Excel 2003 was used to build database, and SPSS 13.0 was used for analyses.
Results:
1. TRB3 genotype frequencies of QQ, QR, RR were 0.662, 0.689; 0.308, 0.292 and 0.031, 0.019 in normal control group and type 2 diabetes mellitus group respectively. The allele frequencies of Q and R were 0.815, 0.185, and 0.835, 0.165 in normal control group and type 2 diabetes mellitus group respectively.
2. In normal control group, the subjects with R84 genetype had the significant increased levels of FINS, HOMA-IR and TG compared with those carrying QQ genetype; and the subjects with R84 genetype had the significant decreased levels of LnISI compared with those carrying QQ genetype (both P<0.05)
3. In type 2 diabetes mellitus group, the patients carrying R84 genetype had the significant increased levels of FINS, HOMA-IR and TG compared with those who carrying QQ genetype; the patients carrying QQ genetype had the significant increased levels of LnISI and TC compared with those who carrying R84 genetype (both P<0.05).
Conclusions:
1. There is the polymorphism of Q84R in TRB3 gene in Chinese Han population.
2. The Q84R polymorphism of TRB3 gene is not associated with the incidence of type 2 diabetes in Chinese Han population.
3. The Q84R polymorphism of TRB3 gene is associated with the levels of fasting insulin and insulin resistance both in diabetes patients and in non-diabetes people in Chinese Han population.
4. The Q84R polymorphism of TRB3 gene is associated with the levels of triglyceride both in diabetes patients and in non-diabetes people in Chinese Han population, and is associated with the levels of total cholesterol in diabetes patients.
方法:随机选取汉族2型糖尿病患者106例,均来自甘肃省人民医院内分泌科住院部。汉族正常对照130例,来自甘肃省人民医院健康体检中心健康体检者,排除糖尿病,且无糖尿病家族史。用酚/氯仿法提取外周血基因组DNA,聚合酶链式反应(PCR)扩增目的DNA。采用连接酶检测反应(LDR)检测TRB3基因Q84R多态性。同时测量身高、体重、腰围、臀围,用全自动生化分析仪测定血浆总胆固醇、甘油三脂、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、空腹血糖,糖化血红蛋白分析仪测定HbA1c,放射免疫法测定空腹胰岛素;用公式计算HOMA胰岛素抵抗指数(HOMA-IR=FPG×FINS/22.5);用胰岛素敏感指数(ISI=1/FPG×FINS)来评价胰岛素敏感性;采用微软办公软件Excel 2003建立数据库,SPSS13.0软件进行统计学分析。
结果:(1)TRB3基因Q84R位点QQ、QR和RR三种基因型频率在正常对照组和2型糖尿病组分别为0.662、0.689;0.308、0.292和0.031、0.019;两组间QQ、QR与RR三种基因型频率进行比较,差异无统计意义(P＞0.05);(2)等位基因Q、R频率在正常对照组和2型糖尿病组分别为0.815、0.185和0.835、0.165,两组间比较差异无统计意义(P＞0.05);(3)正常对照组不同基因型间各临床特征之间的比较,R84基因型受试者的FINS、HOMA-IR和TG水平明显高于QQ基因型受试者,R84基因型的受试者LnISI水平明显低于QQ基因型受试者,且差异均有统计意义(P＜0.05);(4)2型糖尿病组不同基因型间各临床特征之间的比较,R84基因型受试者的FINS、HOMA-IR和TG水平明显高于QQ基因型受试者,R84基因型的受试者LnISI和TC水平明显低于QQ基因型受试者,且差异均有统计意义(P＜0.05)。
结论:(1)中国汉族存在TRB3基因Q84R位点多态性;(2)TRB3基因Q84R位点多态性与中国汉族2型糖尿病的发生无关;(3)TRB3基因Q84R位点多态性与中国汉族糖尿病和非糖尿病人群的空腹胰岛素水平和胰岛素抵抗相关;(4)TRB3基因Q84R位点多态性与中国汉族糖尿病和非糖尿病人群的甘油三酯水平相关,与糖尿病患者的总胆固醇水平相关。
Objectives: To investigate the association of TRB3 gene Q84R polymorphism with type 2 diabetes mellitus in Chinese Han population.
Methods: 106 type 2 diabetes patients were selected at random from our ward in Gansu Provincial People's Hospital. The control group was consisted of 130 subjects from Medical Examination Center (MEC) of Gansu Provincial People's Hospital, without diabetes mellitus and family history of diabetes. Total Genomic DNA from peripheral blood was extracted by Phenol/chloroform method. Target DNA was amplified by the Polymerase Chain Reaction (PCR) and the SNP Q84R in TRB3 gene was detected by ligase detection reaction (LDR). At the same time, we measured the body height, body weight, waist circumference, hip circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP). Total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and fasting blood glucose levels were determined by automatic biochemistry analyzer. Glycosylated hemoglobin (HbA1c) value was determined by HbA1c analyzer. Fasting insulin concentration was measured using insulin radioimmunoassay kit. The homeostasis model assessment insulin resistance index (HOMA-IR) was calculated by the formula: (fasting glucose [millimoles per liter]×fasting insulin [microunits per milliliter])/22.5. ISI (insulin sensitivity index), 1/FPG×FINS, was used to assess Insulin sensitivity. And Microsoft Office Excel 2003 was used to build database, and SPSS 13.0 was used for analyses.
Results:
1. TRB3 genotype frequencies of QQ, QR, RR were 0.662, 0.689; 0.308, 0.292 and 0.031, 0.019 in normal control group and type 2 diabetes mellitus group respectively. The allele frequencies of Q and R were 0.815, 0.185, and 0.835, 0.165 in normal control group and type 2 diabetes mellitus group respectively.
2. In normal control group, the subjects with R84 genetype had the significant increased levels of FINS, HOMA-IR and TG compared with those carrying QQ genetype; and the subjects with R84 genetype had the significant decreased levels of LnISI compared with those carrying QQ genetype (both P<0.05)
3. In type 2 diabetes mellitus group, the patients carrying R84 genetype had the significant increased levels of FINS, HOMA-IR and TG compared with those who carrying QQ genetype; the patients carrying QQ genetype had the significant increased levels of LnISI and TC compared with those who carrying R84 genetype (both P<0.05).
Conclusions:
1. There is the polymorphism of Q84R in TRB3 gene in Chinese Han population.
2. The Q84R polymorphism of TRB3 gene is not associated with the incidence of type 2 diabetes in Chinese Han population.
3. The Q84R polymorphism of TRB3 gene is associated with the levels of fasting insulin and insulin resistance both in diabetes patients and in non-diabetes people in Chinese Han population.
4. The Q84R polymorphism of TRB3 gene is associated with the levels of triglyceride both in diabetes patients and in non-diabetes people in Chinese Han population, and is associated with the levels of total cholesterol in diabetes patients.
引文
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[1]Whiteman EL,Cho H,Bimbaum MJ.Role of Akt/protein kinase B in metabolism.Trends Endocrinol Metab,2002,13:444-451.
[2]Mayumi-Matsuda K,Kojima S,Suzuki H,et al.Identification of a novel kinase-like gene induced during neuronal cell death.Biochem Biophys Res Commun,1999,258:260-264.
[3]Grosshans J,Wieschaus E.A genetic link between morphogenesis and cell division during formation of the ventral furrow in Drosophila.Cell,2000,101:523-531.
[4]Seher TC,Leptin M.Tribbles,a cell-cycle brake that coordinates proliferation and morphogenesis during Drosophila gastrulation.Curr Biol,2000,10:623-629.
[5]Mata J,Curado S,Ephrussi A,et al.Tribbles coordinates mitosis and morphogenesis in Drosophila by regulating string/CDC25 proteolysis.Cell,2000,101:511-522.
[6]Tang K,Finley RL Jr,Nie D,et al.Identification of 12-1ipoxygenase interaction with cellular proteins by yeast two-hybrid screening.Biochemistry,2000,39:3185-3191.
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