脂联素基因启动子的单核苷酸多态性（SNPs）、低脂联素血症和糖尿病之间的关联性研究
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摘要
[背景]脂联素是一种由3T3-L1脂肪细胞分泌的脂泌素。应用不同方法,脂联素被四个机构所确认,所以脂联素又被称为:ACRP30、adipoQ、APM1和GBP28。脂联素在结构上属于C1Q家族,由244个氨基酸组成,包括4个域。N端信号肽含有18个氨基酸,用于组成不同的寡聚体;可变域含有23个氨基酸,是最大的区分各物种的氨基酸序列;胶原域含有66个氨基酸,在结构上与胶原类似;C端球状域含有137个氨基酸,是与效应物结合的受体。[目的]本研究旨在揭示:1、导致低脂联素血症的环境因素和遗传因素;2、从低脂联素血症到糖尿病的机制;3、低脂联素血症引起的糖尿病的诊断和治疗。[方法]共有186名汉族个体被纳入到本研究之中,包括81名男性和105名女性,在延边生活至少5年。检测了他们的总胆固醇(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)、空腹血浆葡萄糖(FPG)、空腹血浆胰岛素(FPI)、血浆脂联素(PA)。利用PCR和测序筛选单核苷酸多态性(SNP)。ANOVA和回归用于分析数据间的关系。[结果]PA和位于脂联素基因启动子上的2个SNP:-11426A＞G和11377C＞G及其构成的基因型和单倍型之间没有统计学意义。PA与体重指数(BMI)成反比(b=-0.17)。FPI与PA成正比(b=1.19)。HDL-C与PA成正比(b=0.03)。60%的低脂联素血症患者患有糖尿病,同时69%的糖尿病患者是由低脂联素血症引起。FPI在单纯低脂联素血症组和低脂联素血症引起的糖尿病组明显低于正常组(p=0.021和p＜0.001)。胰岛素抵抗指数(HOMA-IR)在其它原因引起的糖尿病组明显高于正常组(p＜0.001)。但是HOMA-IR在低脂联素血症引起的糖尿病组和正常组之间没有统计学意义(p=0.093)。[结论]1、肥胖可以降低血浆脂联素水平;2、脂联素可以刺激高密度脂蛋白和胰岛素分泌并且低胰岛素血症是低脂联素血症引起的糖尿病的直接原因;3、FPG≥7.0 mmol/l和PA＜4.68μg/ml可以作为在延边汉族人中低脂联素血症引起的糖尿病的诊断标准以及低脂联素血症引起的糖尿病的相应的治疗途径。
This study was going to investigate: 1. Environmental and genetic factors leading to hypoadiponectinemia; 2. Mechanism from hypoadiponectinemia to diabetes; 3. Diagnosis and treatment of hypoadiponectinemia-derived diabetes. A total of 186 subjects were involved in this study, including 81 men and 105 women. They were all Chinese and lived in Yanbian for at least 5 years. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), Fasting plasma glucose (FPG), fasting plasma insulin (FPI), and plasma adiponectin (PA) were measured. PCR and sequencing were used for screening of single nucleotide polymorphisms (SNPs). ANOVA and regression were used for analysis of relations of data. No significant difference of PA between genotypes or haplotypes of SNPs of -11426A>G and -11377C>G which are on the promoter of adipoctin gene. PA was inversely proportional to body mass index (BMI) (b = -0.17). FPI was directly proportional to PA (b = 1.19). HDL-C is directly proportional to PA (b = 0.03). 60% of hypoadiponectinemia patients suffered from diabetes and 69% of diabetic patients were hypoadiponectinemia-derived diabetic patients. FPI in simple hypoadiponectinemia group and in hypoadiponectinemia-derived diabetic group was significantly lower than in normal group (p = 0.021 and p < 0.001 respectively). Homeostasis model assessment of insulin resistance (HOMA-IR) in other cause-derived diabetic group was significantly higher than in normal group (p < 0.001). But there was no significant difference of HOMA-IR between hypoadiponectinemia-derived diabetic group and normal group (p = 0.093). Following conclusions had been drawn: 1. Obesity could decrease adiponectnemia. 2. Adiponectin could stimulate HDL and insulin secretion and the hypoinsulinemia was the direct cause of hypoadiponectinemia-derived diabetes. 3. FPG≥7.0 mmol/l and PA < 4.68μg/ml could be the diagnosis criterion of hypoadiponectinemia-derived diabetes in Yanbian Chinese and the relative ways to treat the hypoadiponectinemia-derived diabetes.
This study was going to investigate: 1. Environmental and genetic factors leading to hypoadiponectinemia; 2. Mechanism from hypoadiponectinemia to diabetes; 3. Diagnosis and treatment of hypoadiponectinemia-derived diabetes. A total of 186 subjects were involved in this study, including 81 men and 105 women. They were all Chinese and lived in Yanbian for at least 5 years. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), Fasting plasma glucose (FPG), fasting plasma insulin (FPI), and plasma adiponectin (PA) were measured. PCR and sequencing were used for screening of single nucleotide polymorphisms (SNPs). ANOVA and regression were used for analysis of relations of data. No significant difference of PA between genotypes or haplotypes of SNPs of -11426A>G and -11377C>G which are on the promoter of adipoctin gene. PA was inversely proportional to body mass index (BMI) (b = -0.17). FPI was directly proportional to PA (b = 1.19). HDL-C is directly proportional to PA (b = 0.03). 60% of hypoadiponectinemia patients suffered from diabetes and 69% of diabetic patients were hypoadiponectinemia-derived diabetic patients. FPI in simple hypoadiponectinemia group and in hypoadiponectinemia-derived diabetic group was significantly lower than in normal group (p = 0.021 and p < 0.001 respectively). Homeostasis model assessment of insulin resistance (HOMA-IR) in other cause-derived diabetic group was significantly higher than in normal group (p < 0.001). But there was no significant difference of HOMA-IR between hypoadiponectinemia-derived diabetic group and normal group (p = 0.093). Following conclusions had been drawn: 1. Obesity could decrease adiponectnemia. 2. Adiponectin could stimulate HDL and insulin secretion and the hypoinsulinemia was the direct cause of hypoadiponectinemia-derived diabetes. 3. FPG≥7.0 mmol/l and PA < 4.68μg/ml could be the diagnosis criterion of hypoadiponectinemia-derived diabetes in Yanbian Chinese and the relative ways to treat the hypoadiponectinemia-derived diabetes.
引文
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