Learn More
The onset of type 2 diabetes (T2DM) is preceded by obesity, insulin resistance, and impaired beta-cell function. Uncoupling protein-2 (UCP2) is a widely expressed inner mitochondrial membrane protein. Common polymorphisms of the UCP2 gene have been implicated in diabetes, in obesity, and with changes in UCP2 mRNA levels. We tested the hypothesis that common(More)
OBJECTIVE We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes diagnosis, and BMI. RESEARCH DESIGN AND METHODS After removing outliers and problematic samples, we conducted linkage analysis using 5,914 SNPs in 1,344 individuals from 530(More)
OBJECTIVE To determine altered gene expression profiles in subcutaneous adipose and skeletal muscle from nondiabetic, insulin-resistant individuals compared with insulin-sensitive individuals matched for BMI. RESEARCH DESIGN AND METHODS A total of 62 nondiabetic individuals were chosen for extremes of insulin sensitivity (31 insulin-resistant and 31(More)
Insulin resistance is strongly associated with obesity, but even among obese subjects insulin sensitivity varies widely. Recently, a new adipocyte hormone, resistin, was identified, shown to reduce insulin-mediated glucose uptake, and shown to be increased in obese mice. We used the chromosome 19 draft sequence to determine the genomic structure of human(More)
OBJECTIVE Linkage of the chromosome 1q21-25 region to type 2 diabetes has been demonstrated in multiple ethnic groups. We performed common variant fine-mapping across a 23-Mb interval in a multiethnic sample to search for variants responsible for this linkage signal. RESEARCH DESIGN AND METHODS In all, 5,290 single nucleotide polymorphisms (SNPs) were(More)
The calpain-10 gene (CAPN10) has been implicated in type 2 diabetes (T2DM) susceptibility by both linkage and association in a Hispanic population from Starr County Texas. Common intronic variants seem to alter CAPN10 mRNA levels and were associated with insulin resistance but not diabetes in Pima Indians. The role of these variants in Caucasian populations(More)
BACKGROUND Defective insulin secretion is a key defect in the pathogenesis of type 2 diabetes (T2DM). The beta-cell specific transcription factor, insulin promoter factor 1 gene (IPF1), is essential to pancreatic development and the maintenance of beta-cell mass. We hypothesized that regulatory or coding variants in IPF1 contribute to defective insulin(More)
Prior type 2 diabetes (T2D) genome-wide association studies (GWASs) have generated a list of well-replicated susceptibility loci in populations of European and Asian ancestry. To validate the trans-ethnic contribution of the single-nucleotide polymorphisms (SNPs) involved in these GWASs, we performed a family-based association analysis of 32 selected GWAS(More)
The risk of type 2 diabetes (T2D) increases with obesity. One possible explanation is that pleiotropic genes affect risk of both T2D and obesity. To identify pleiotropic genes, we performed bivariate analysis of T2D with waist-hip ratio (WHR) and with body mass index (BMI) in the African-American subset of the Genetics of NIDDM (GENNID) sample. Of 12 T2D(More)
Twin and family studies have demonstrated a strong genetic component to type 2 diabetes mellitus (T2DM), but mapping the susceptibility genes that account for this risk has proved difficult. At least seven single gene defects are known to cause T2DM, often with early onset and insulin deficiency, but these causes account for 5% or less of all T2DM. A large(More)