A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome
A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome
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DOI：
10.2337/diabetes.51.7.2306
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发表时间：
2002-07-01
期刊：
影响因子：
7.7
通讯作者：
Doria, A
中科院分区：
文献类型：
--
作者：
Menzaghi, C;Ercolino, T;Doria, A
脂联素是一种由脂肪细胞分泌的调节胰岛素作用的蛋白质。为了评估该基因的变异是否与白种人胰岛素抵抗的流行有关，我们对413名非糖尿病患者进行了该位点的两个单核苷酸多态性（snp）基因分型。选择这两个snp （45T- b> G和276G- >T）是因为它们与日本2型糖尿病有关。虽然每种多态性都与胰岛素抵抗相关，但两者共同定义的单倍型与胰岛素抵抗综合征的许多成分密切相关。风险单倍型的纯合子具有较高的体重（P = 0.03）、腰围（P = 0.004）、收缩压（P = 0.01）和舒张压（P = 0.003）、空腹血糖（P = 0.02）和胰岛素（P = 0.005）水平、胰岛素抵抗的稳态模型评估（HOMA） （P = 0.003）和总胆固醇/高密度脂蛋白胆固醇比值（P = 0.01）。纯合子的血浆脂联素水平也显著降低（P = 0.03），与性别、年龄和体重无关。在一个由614名高加索人组成的独立研究小组中，包括310名2型糖尿病患者，风险单倍型被证实与体重增加有关（P = 0.03），但与2型糖尿病本身无关。我们得出结论，脂联素位点的变异与肥胖和胰岛素抵抗综合征的其他特征有关，但考虑到这两个snp的性质，风险单倍型最有可能是连锁不平衡的标记，其多态性影响血浆脂联素水平和胰岛素敏感性。
Adiponectin is a protein secreted by adipocytes that modulates insulin action. To assess whether variants of this gene contribute to the prevalence of insulin resistance in Caucasians, we genotyped 413 nondiabetic individuals for two single nucleotide polymorphisms (SNPs) at this locus. The two SNPs (45T-->G and 276G-->T) were chosen because of their association with type 2 diabetes in Japanese. Whereas each polymorphism was significantly associated with some correlate of insulin resistance, the haplotype defined by the two together was strongly associated with many components of the insulin resistance syndrome. Homozygotes for the risk haplotype had higher body weight (P = 0.03), waist circumference (P = 0.004), systolic (P = 0.01) and diastolic (P = 0.003) blood pressure, fasting glucose (P = 0.02) and insulin (P = 0.005) levels, homeostasis model assessment (HOMA) for insulin resistance (P = 0.003), and total to HDL cholesterol ratio (P = 0.01). Homozygotes also had significantly lower plasma levels of adiponectin (P = 0.03), independent of sex, age, and body weight. In an independent study group of 614 Caucasians, including 310 with type 2 diabetes, the risk haplotype was confirmed to be associated with increased body weight (P = 0.03) but not with type 2 diabetes per se. We conclude that variability at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome, but given the nature of the two SNPs, the risk haplotype is most probably a marker in linkage disequilibrium with an as yet unidentified polymorphism that affects plasma adiponectin levels and insulin sensitivity.