兰州大学机构库 >学院待认领
AMPKα2基因多态性与2型糖尿病及脂联素、抵抗素相关性研究
Alternative TitleCorrelation between AMPKα2 subunit gene polymorphism and type 2 diabetes mellitus, adiponectin and resistin
刘婧星
Thesis Advisor任建功
2011-05-18
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword腺苷酸活化蛋白激酶 2型糖尿病 抵抗素 脂联素
Abstract目的 通过研究甘肃地区汉族健康人群和2型糖尿病(T2DM)患者中腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)α2基因单核苷酸多态性(SNPs)rs2796516位点的基因型分布情况,探讨AMPKα2基因多态性与2型糖尿病、胰岛素抵抗及血清脂联素、抵抗素水平的关系。 方法 选取甘肃地区T2DM患者188例(病例组)和非糖尿病正常人群179例(对照组)。所有研究对象测量身高、体重、血压,计算体重指数(BMI) =体重/身高2(kg/m2),并留取空腹和早餐后2h血样用于提取基因组DNA及测定生化指标。采用全自动生化分析仪测定各组的血糖、血脂等代谢指标;采用放射免疫法检测空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR)=空腹血糖(FPG) ×空腹胰岛素(FINS) /22.5和胰岛素分泌指数(HOMA-IS)=20×空腹胰岛素/(空腹血糖-3.5),用以评价胰岛素抵抗水平和胰岛β细胞功能;应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法,检测AMPK-rs2796516 G/A基因型,计算并分析两组人群等位基因频率的差异;采用酶联免疫吸附法(ELISA)测定血清脂联素、抵抗素水平。 结果 (1)病例组和对照组中均存在AMPK- rs2796516位点G/A基因突变,该位点G/G、G/A、A/A的基因频率在病例组分别为51.1%、32.4%、16.5%,A等位基因频率为32.7%,在对照组分别为76.0%、17.9%和6.1%,A等位基因频率为15.1%,二组间基因型构成比及等位基因频率的差异均有统计学意义(p<0.01)。(2)T2DM患者中AMPK-rs2796516 G/A基因多态性与胰岛素抵抗明显相关,与G/G和G/A组相比,A/A基因型患者空腹胰岛素分泌水平明显降低,HOMA-IR明显升高 (p<0.01)。(3)T2DM患者中AMPK-rs2796516 G/A基因多态性与血脂代谢相关。与G/G和G/A基因型相比,A/A基因型患者TG、TC、LDL较高(p<0.05)。(4)病例组中基因多态性与血清脂联素、抵抗素水平明显相关,其中A/A组中,血清脂联素最低,抵抗素最高,三组间差别有显著性(p<0.01)。 结论 (1)甘肃地区人群中AMPK-rs2796516具有多态性频率分布特点,AMPK-rs 2796516基因多态性与T2DM的发生有相关性,A/A基因型患者空腹及餐后血糖较高,血脂水平较高,胰岛素抵抗加重,推测A等位基因可能是糖尿病易感基因,而G等位基因可能是糖尿病保护基因。(2)AMPK-rs2796516基因多态性与T2DM患者血清脂联素、抵抗素水平有显著相关性。提示脂联素和抵抗素可能参与了胰岛素抵抗,在T2DM的发病过程中起到了一定作用。
Other AbstractObjective To study the genotype distribution of a single nucleotide polymorphism (SNP) rs-2796516(G>A) in 5’-AMP-activated protein kinase(AMPK) alpha-2 subunit gene (PRKAA2) in gansu area. To investigate the association between PRKAA2 polymorphism and type 2 diabetes mellitus(T2DM), insulin resistance(IR) and plasma resistin and adiponectin. Methods In this study, 188 patientes with T2DM(case group) and 179 healthy persons(control group) from gansu area were enrolled. Height, weight, blood pressure, Body mass index (BMI), plasma glucose, serum insulin and lipid profile were measured. Homeostasis model assessment of insulin resistance(HOMA-IR) and insulin secretion(HOMA-IS) were used to estimate insulin resistance and β-cell function. A SNP rs-2796516(G>A) in PRKAA2 was genotyped in all the subjects enrolled using PCR and restriction fragment length polymorphism(RFLP). ELISA technique were employed to determine the plasma adiponectin and resistin concentration. Results (1)There was polymorphism of AMPK-rs2796516 in both T2DM and normal subjects. The distribution of AMPK-rs2796516 G/G,G/A and A/A genotypes:DM group was 51.1%,32.4%,16.5%, respectively, A allele frequency was 32.7%;control group was 76.0%,17.9% ,6.1%, respectively, A allele frequency was 15.1%. There was significant difference of genotype constituent ratio and A allele frequency in two groups(p<0.01). (2) In case group, PRKAA2 polymorphism were significantly related to insulin resistance, AMPK- rs2796516 A/A genotype had lower FINS and higher HOMA-IR than G/G and G/A genotype(p<0.01). (3) There was association between the polymorphism of AMPK- rs2796516 and dyslipidemia in type 2 diabetes. AMPK-rs2796516 A/A genotype had higher concentration of serum TG, TC and LDL than G/G and G/A genotype (p<0.05). (4) There was association between the polymorphism of AMPK-rs2796516 and the concentration of plasma adiponectin and resistin. Compared with GG and GA group, the concentration of serum resistin were higher in AA group, the concentration of serum adiponectin was lower in AA group(p<0.01). Conclusion (1) The polymorphism of AMPK-rs2796516 G/A existed among Gansu population, and it was relelant with T2DM, AMPK-rs2796516 A/A genotype had higher FPG,2hPG, lipid level, It was presumed that A allele maybe the risk gene of T2DM; G allele maybe the protecting gene. (2) There was significant association between the polymorphism of AMPK-rs 2796516 and the concentration of plasma adiponect...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/224235
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
刘婧星. AMPKα2基因多态性与2型糖尿病及脂联素、抵抗素相关性研究[D]. 兰州. 兰州大学,2011.
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