肥胖患者脂联素基因第45位点单核苷酸多态性与血浆脂联素水平及胰岛素抵抗的相关性研究

Association of single nucleotide polymorphism at position 45 in adiponectin gene with plasma adiponectin level and insulin resistance in obesity

  • 摘要:
    目的 研究福建省泉州地区汉族肥胖人群脂联素基因第45位点单核苷酸多态性(SNP45)与血浆脂联素水平及胰岛素抵抗的关系。
    方法 随机选择肥胖症患者248例,正常对照者223例,采用液相平衡竞争放射免疫分析法测定血浆中空腹胰岛素(FINS)水平;利用自动生化分析仪测定空腹血糖(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)水平;计算体重指数(BMI)、腰臀比、稳态模型胰岛素抵抗指数(HOMA-IR);采用酶联免疫吸附试验测定空腹血浆脂联素水平;采用PCR-限制性片段长度多态性技术检测脂联素基因SNP45。
    结果 ① 肥胖症组和正常对照组脂联素基因SNP45的GT+GG基因型的分布分别为61%和44%(χ2=14.182,P<0.01),G等位基因频率分别为35%和25%(χ2=10.708,P<0.01)。②肥胖症组中,脂联素基因SNP45的GG+GT型与TT型相比,前者的TG、LDL-C水平(t=2.604, P<0.01; t=5.507, P<0.01)升高,而脂联素和HDL-C水平(t=2.275,P<0.05;t=10.100,P<0.01)降低。③正常对照组中,脂联素基因SNP45的GG+GT型与TT型相比,前者的脂联素、TG、TC水平(t=2.510,P<0.05; t=2.922,P<0.01; t=3.272,P<0.01)显著低于后者。④以脂联素基因SNP45为因变量进行Logistic回归分析,肥胖症组中脂联素基因SNP45的GG+GT型与TT型相比,GG+GT型血清脂联素水平减少(OR=0.810,95%CI:0.673~0.975,P<0.05),胰岛素抵抗风险增加(OR=1.746,95%CI:1.060~2.875,P<0.05);正常组中GG+GT型胰岛素抵抗风险增加(OR=3.962,95%CI:1.089~14.411,P<0.05)。
    结论 ① 脂联素基因SNP45的基因型和等位基因频率在肥胖症组与正常对照组中的分布有显著性差异。②脂联素基因SNP45与肥胖症患者的胰岛素抵抗及血脂水平相关。③肥胖症组中脂联素基因SNP45与脂联素水平相关。

     

    Abstract:
    Objective To explore the association of single nucleotide polymorphism at position 45(SNP45) in adiponectin gene with plasma adiponectin level and insulin resistance in obesity in Quanzhou area of Fujian province.
    Methods Two hundred and forty-eight patients with obesity and 225 normal control subjects were enrolled in this study. Fasting insulin(FINS) were measured by radioimmunoassay and fasting plasma glucose(FPG), total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol(LDL-C) were measured by BECKMAN DXC800 biochemistry analyzer. Body mass index(BMI), waist to hip ratio, homeostasis model assessment of insulin resistance(HOMA-IR) were calculated. Plasma adiponectin levels were examined by means of enzyme-linked immunosorbentassy. The adiponectin gene SNP45 was identified by PCR-restriction fragment length polymorphism.
    Results ① Frequencies of GG+GT genotype in obesity group and normal control group were 61% and 44%respectively(χ2=14.182, P < 0.01), and G allele frequencies were 35% and 25%(χ2=10.708, P < 0.01). ②In obesity group, the subjects with SNP45 GG+GT genotype had higher TG and LDL-C levels than those with TT genotype(t=2.604, P < 0.01; t=5.507, P < 0.01), and had lower adiponectin level than those with TT genotype(t=2.275, P < 0.05), and had significantly lower HDL-L level than those with TT genotype(t=10.100, P < 0.01). ③In normal control group, the subjects with SNP45 GG+GT genotype had significantly lower adiponectin, TG, TC levels than those with TT genotype(t=2.510, P < 0.05; t=2.922, P < 0.01; t=3.272, P < 0.01). ④Logistic analysis proved that the SNP45 GG+GT genotype in obesity group was associated with decreased risk of plasma adiponectin level(OR=0.810, 95%CI: 0.673-0.975, P < 0.05), and with increased risk of HOMA-IR(OR=1.746, 95%CI: 1.060-2.875, P < 0.05). The SNP45 GG+GT genotype in normal control group was associated with increased risk of HOMA-IR(OR=3.962, 95%CI: 1.089-14.411, P < 0.05).
    Conclusions ① The distribution of adiponection of genotype and allele frequencies of the SNP45 were different in obesity and normal control groups. ②The SNP45 in adiponectin was associated with obesity, insulin resistance and the total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein levels. ③The SNP45 in adiponectin was associated with the fasting adiponectin levels in obesity group.

     

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