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首页> 外文期刊>Disease markers >Analysis of osteocalcin as a candidate gene for type 2 diabetes (T2D) and intermediate traits in Caucasians and African Americans.
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Analysis of osteocalcin as a candidate gene for type 2 diabetes (T2D) and intermediate traits in Caucasians and African Americans.

机译：分析骨钙素作为高加索人和非裔美国人的2型糖尿病（T2D）和中间性状的候选基因。

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Recent studies in mice and human identified osteocalcin (OCN) as a bone-derived hormone that modulates insulin secretion and insulin sensitivity. OCN is synthesized by the bone gamma-carboxyglutamate protein (BGLAP) gene located in the well replicated region of type 2 diabetes (T2D) linkage on chromosome 1q22. We resequenced BGLAP gene in 192 individuals with T2D and performed case-control studies in 766 Caucasian (461 T2D and 305 controls) and 563 African American individuals (371 T2D and 192 controls). Metabolic effects of BGLAP variants were examined in 127 nondiabetic members of Caucasian T2D families and in 498 unrelated nondiabetic African American and Caucasian individuals. BGLAP expression was tested in transformed lymphocytes from 60 Caucasian individuals. We identified 17 single nucleotide polymorphisms (SNPs) in African Americans, but observed only the two known SNPs in Caucasians. No SNP was associated with T2D. Promoter SNP rs1800247 was not associated with metabolic traits including insulin sensitivity (S(I)) or fasting glucose in either population, but nonsynonymous SNP rs34702397 (R94Q) was nominally associated with S(I) (uncorrected p=0.05) and glucose-mediated glucose disposal (S(G); uncorrected p=0.03) in African Americans. No SNP altered measures of insulin secretion or obesity, nor was BGLAP expression associated with rs1800247. Our study was sufficiently powered to exclude BGLAP variants as a major risk factor (OR > 1.5) for T2D in Caucasians, but coding variants in exon 4 may alter glucose homeostasis and diabetes risk in African Americans.
机译：最近在小鼠和人类中进行的研究确定骨钙素（OCN）是一种可调节胰岛素分泌和胰岛素敏感性的骨源激素。 OCN由位于染色体1q22上2型糖尿病（T2D）连锁的复制良好的区域中的骨γ-羧基谷氨酸蛋白（BGLAP）基因合成。我们在192名T2D患者中对BGLAP基因进行了重新测序，并在766名白种人（461名T2D和305名对照）和563名非裔美国人（371名T2D和192名对照）中进行了病例对照研究。 BGLAP变体的代谢作用在高加索T2D家庭的127位非糖尿病成员以及498位无关联的非糖尿病非裔美国人和高加索个体中进行了检查。在来自60名白人个体的转化淋巴细胞中测试了BGLAP表达。我们在非洲裔美国人中发现了17个单核苷酸多态性（SNP），但在高加索人中仅观察到两个已知的SNP。没有SNP与T2D相关。在任一人群中，启动子SNP rs1800247与包括胰岛素敏感性（S（I））或禁食葡萄糖在内的代谢性状均不相关，但名义上非同义的SNP rs34702397（R94Q）与S（I）相关（未校正p = 0.05）和葡萄糖介导非洲裔美国人的葡萄糖处置（S（G）;未校正p = 0.03）。没有SNP改变胰岛素分泌或肥胖的措施，也没有BGLAP表达与rs1800247相关。我们的研究有足够的能力将BGLAP变异体排除为高加索人T2D的主要危险因素（OR> 1.5），但外显子4中的编码变异体可能会改变非洲裔美国人的葡萄糖稳态和糖尿病风险。

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