Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls ≥45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a ∼1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 × 10−8, which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic β-cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians.

The electrochemistry of trithiocarbonates and trithiocarbenium ions has been studied in nonaqueous solvents, mainly in acetonitrile. Trithiocarbonates are reduced to the corresponding radical anions which undergo further chemical reactions. Anodic oxidation of trithiocarbonates leads to coupling products, but does not provide synthetic entry into the tetrathioethylenes. The latter class of compounds is available by a procedure which involves reductive coupling of trithiocarbenium cations, followed by pyrolysis of the resulting orthothiooxalates. The mechanism of the dimerization reaction appears to involve a simple radical‐radical coupling (DIMI mechanism). Details of the synthetic procedure are given along with voltammetric data for six trithiocarbonates and eighteen trithiocarbenium ions.

Prior results from our genomic scan in Pima Indians indicated an obesity locus in a region on chromosome 11q23‐24 that was also linked to diabetes. Bivariate linkage analysis for the combined phenotype “diabesity” gave the strongest evidence for linkage (LOD = 5.2). Our aim is to positionally clone the gene(s) responsible for the linkage. Linkage disequilibrium mapping is being used to narrow the chromosomal region. Single nucleotide polymorphisms (SNPs) are being systematically identified and genotyped at 50‐kb intervals across the region of linkage. To date, 455 SNPs have been genotyped in 1229 Pimas. A region containing a cluster of SNPs strongly associated with BMI and a second region, approximately 2 Mb telomeric, containing a cluster of SNPs associated with diabetes have been preliminarily identified.