João Fadista, Petter Vikman, Emilia Ottosson Laakso, Inês Guerra Mollet, Jonathan Lou Esguerra, Jalal Taneera, Petter Storm, Peter Osmark, Claes Ladenvall, Rashmi B Prasad, Karin B Hansson, Francesca Finotello, Kristina Uvebrant, Jones K Ofori, Barbara Di Camillo, Ulrika Krus, Corrado M Cilio, Ola Hansson, Lena Eliasson, Anders H Rosengren, Erik Renström, Claes B Wollheim, Leif Groop
Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion...
September 23, 2014: Proceedings of the National Academy of Sciences of the United States of America