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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD000198-07
Application #
7632066
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
7
Fiscal Year
2008
Total Cost
$297,329
Indirect Cost
Name
Howard University
Department
Type
DUNS #
056282296
City
Washington
State
DC
Country
United States
Zip Code
20059
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