GENETIC RISK FACTORS FOR METABOLIC SYNDROME IN MINORITY POPULATIONS

代谢综合征，以及相关的2型糖尿病，已成为一种流行病，在所有的“西化”， 世界文化，少数民族面临的风险最大。虽然被认为是一种中年疾病， 儿科人群的发病率正在迅速增加。CDC目前的风险估计预测， 2000年出生的儿童将有50%的风险患上2型糖尿病，平均损失20岁。 调整生活质量。快速增加是由于不活动，容易获得高热量的食物， 然而，五个组成风险因素（血液）中的每一个都有显着的遗传贡献。 血压、血糖指数、HDL、LDL、腰围）。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， 对目标人群进行干预。 我们目前的初步数据识别的第一个主要代谢综合征的风险遗传位点。一 15kb的单倍型被鉴定为含有多个SNP，每个SNP在进化上保守的调节基因中， 地区单倍型2同时改变了三个区域，远离进化保守的祖先 顺序对6个受试者组群（总共9，200个个体）的该单倍型的测试显示单倍型2 提供了对代谢综合征的保护（相对风险RR=0.5 p<0.0001）。我们发现了很多 与该基因座相关的其它表型包括肌肉力量、骨体积、肥胖， 循环胰岛素、循环葡萄糖和胰岛素抵抗。我们还表明， SNPs在骨、肌肉和脂肪细胞中差异性地改变增强子和抑制子功能。

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.