Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

Glucose stimulation of cytochrome C reduction and oxygen consumption as assessment of human islet quality.

BACKGROUND: An in vitro method to assess human islets could prevent transplantation of nonviable islets and facilitate the optimization of islet preparation. We hypothesize that glucose-stimulated cytochrome c reduction and oxygen consumption by human islets can be used as predictors of transplant success. METHODS: Isolated human islets were obtained from research-grade pancreata. Using a previously developed islet flow culture system, the response of cytochrome c reduction and oxygen consumption to glucose was compared to the ability of islets transplanted into nondiabetic NOD-SCID mice to secrete C-peptide in response to a glucose tolerance test conducted 7 days following transplant (n=10). RESULTS: In vitro responses by human islets were qualitatively similar to those seen in rat islets: glucose increased both oxygen consumption and cytochrome c reduction. However, the responses were smaller in magnitude and quite variable. Scatter plots of C-peptide and quantiles for ln(C-peptide) indicated that 12 ng/ml could be used as threshold of transplant success with which to evaluate the diagnostic potential of cytochrome c and oxygen consumption. Data was analyzed by generating receiver operating curves and the area under the curve was 0.889 (95% CI: 0.645-1.000) and 0.738 (95% CI: 0.413-1.000) for cytochrome c reduction and oxygen consumption respectively (1 indicates absolute predictive capability and 0.5 indicates no predictive capability). CONCLUSIONS: The detection of glucose-stimulated cytochrome c reduction and oxygen consumption may have utility as criteria for the assessment of human islet quality.