GENETIC RISK FACTORS FOR METABOLIC SYNDROME IN MINORITY POPULATIONS

代谢综合征，以及与之相关的2型糖尿病，已经成为所有西方人的流行病。 世界文化，少数群体面临着最大的风险。虽然被认为是中年疾病， 儿科人群中的发病率正在迅速增加。疾控中心目前的风险估计预测 2000年出生的儿童患2型糖尿病的风险为50%，平均损失20岁。 品质调整后的生活。快速增加是由于缺乏运动和容易获得高卡路里食物， 然而，五个风险因素(血液)中的每一个都有显着的遗传贡献 血压、血糖指数、高密度脂蛋白、低密度脂蛋白、腰围)。对遗传风险因素的识别被认为是 这对于理解易感性的生物学特性很重要，也有助于更个性化 对目标人群的干预。 我们提供了识别第一个主要代谢综合征风险基因座的初步数据。一个 鉴定出含有多个SNP的15kb单倍型，每个SNP在进化上保守的调控 地区。单倍型2同时改变了进化保守的祖先的三个区域 序列。对6个受试者队列，总计9,200个个体的测试表明，单倍型2 提供对代谢综合征的保护(相对风险RR=0.5p&lt；0.0001)。我们发现了很多 与该基因座相关的其他表型，包括肌肉力量、骨体积、肥胖、 循环胰岛素、循环葡萄糖和胰岛素抵抗。我们还展示了组件 SNPs在骨骼、肌肉和脂肪细胞中以不同的方式改变增强子和抑制子的功能。

Metabolic syndrome, and the associated type 2 diabetes, has become an epidemic in all "westernized" world cultures, with minority populations at the greatest risk. While considered a disease of mid-age, incidence in pediatric populations is rapidly increasing. Current risk estimates by the CDC predict that children bom in 2000 will have a 50% risk of developing type 2 diabetes, with an average loss of 20 yrs of quality adjusted life. The rapid increases are due to inactivity, and easy availability of calorie-rich food, however there are significant genetic contributions to each of the five component risk factors (blood pressure, glycemic index, HDL, LDL, waist circumference). Identification of genetic risk factors are felt to be important both for understanding of the biology of predispositions, and also to enable more personalized interventions to targeted populations. We present preliminary data on identification of the first major metabolic syndrome risk genetic locus. A 15kb haplotype was identified that contains multiple SNPs, each in evolutionary conserved regulatory regions. Haplotype 2 simultaneously alters three regions away from evolutionary conserved ancestral sequence. Testing of 6 subject cohorts, totaling 9,200 individuals, for this haplotype shows that Haplotype 2 confers protection from metabolic syndrome (relative risk RR=0.5 p<0.0001). We have found many additional phenotypes associated with this locus, including muscle strength, bone volume, adiposity, circulating insulin, circulating glucose, and insulin resistance. We have also shown that the component SNPs alter enhancer and represser function differentially in bone, muscle, and fat cells.