α2-Heremans-Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action
α2-Heremans-Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action
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DOI：
10.1007/s00125-004-1556-7
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发表时间：
2004-11-01
期刊：
影响因子：
8.2
通讯作者：
Arner, P
中科院分区：
文献类型：
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作者：
Dahlman, I;Eriksson, P;Arner, P
目的/假设。本研究的目的是研究编码人α（2）-Heremans-Schmid糖蛋白（AHSG）基因的单核苷酸多态性（SNPs）对肥胖和脂肪细胞胰岛素作用的影响。我们在AHSG中筛选了24个个体的SNP。六个单倍型标记的SNPs基因分型在188瘦和176肥胖，否则健康的妇女，为他们共同的血液化学表型也可。对117名瘦型和174名肥胖女性的脂肪细胞脂解和脂肪生成表型进行定量分析。位于AHSG 5 '区的-469T> G SNP与胰岛素介导的脂解抑制和脂肪生成刺激以及基础和8-溴环AMP刺激的脂解相关。三个AHSG SNPs与循环胆固醇水平相关。六个基因型SNP或推断的单倍型均与BMI、计算的体脂百分比、腰围、葡萄糖或胰岛素的循环水平或胰岛素抵抗的稳态模型评估（用作体内胰岛素敏感性的估计）无关。我们的研究结果与胰岛素抵抗和2型糖尿病易感性的阈值模型一致，其中特定的遗传位点调节中间分子表型。当一个人在这些基因座上的易感等位基因组超过阈值时，就会发生临床疾病。脂肪细胞中的脂解似乎是对AHSG的变化特别敏感的表型。
Aims/hypothesis. The aim of this study was to investigate the effect of single-nucleotide polymorphisms (SNPs) in the gene encoding the human alpha(2)-Heremans-Schmid glycoprotein (AHSG) on obesity and insulin action in adipocytes.Methods. We screened 24 individuals for SNPs in AHSG. Six haplotype-tagging SNPs were genotyped in 188 lean and 176 obese otherwise healthy women for whom common blood chemistry phenotypes were also available. Adipocyte lipolysis and lipogenesis phenotypes were quantified in a subset of 117 lean and 174 obese women.Results. The -469T>G SNP, which is located in the 5' region of AHSG, was associated with insulin-mediated inhibition of lipolysis and stimulation of lipogenesis, as well as basal and 8-bromocyclic AMP-stimulated lipolysis. Three AHSG SNPs were associated with circulating levels of cholesterol. None of the six genotyped SNPs or inferred haplotypes were associated with BMI, calculated percent body fat, waist circumference, circulating levels of glucose or insulin, or homeostasis model assessment of insulin resistance, which was used as an estimate of in vivo insulin sensitivity.Conclusions/interpretation. Our results are in agreement with a threshold model of susceptibility for insulin resistance and type 2 diabetes, in which specific genetic loci regulate intermediate molecular phenotypes. When an individual's set of susceptibility alleles at such loci exceeds a threshold, clinical disease occurs. Lipolysis in adipocytes appears to be a phenotype that is particularly sensitive to variation in AHSG.