Richards, J. Brent and Waterworth, Dawn and O'Rahilly, Stephen and Hivert, Marie-France and Loos, Ruth J. F. and Perry, John R. B. and Tanaka, Toshiko and Timpson, Nicholas John and Semple, Robert K. and Soranzo, Nicole and Song, Kijoung and Rocha, Nuno and Grundberg, Elin and Dupuis, Josee and Florez, Jose C. and Langenberg, Claudia and Prokopenko, Inga and Saxena, Richa and Sladek, Robert and Aulchenko, Yurii and Evans, David and Waeber, Gerard and Erdmann, Jeanette and Burnett, Mary-Susan and Sattar, Naveed and Devaney, Joseph and Willenborg, Christina and Hingorani, Aroon and Witteman, Jaquelin C. M. and Vollenweider, Peter and Glaser, Beate and Hengstenberg, Christian and Ferrucci, Luigi and Melzer, David and Stark, Klaus and Deanfield, John and Winogradow, Janina and Grassl, Martina and Hall, Alistair S. and Egan, Josephine M. and Thompson, John R. and Ricketts, Sally L. and Koenig, Inke R. and Reinhard, Wibke and Grundy, Scott and Wichmann, H-Erich and Barter, Phil and Mahley, Robert and Kesaniemi, Y. Antero and Rader, Daniel J. and Reilly, Muredach P. and Epstein, Stephen E. and Stewart, Alexandre F. R. and Van Duijn, Cornelia M. and Schunkert, Heribert and Burling, Keith and Deloukas, Panos and Pastinen, Tomi and Samani, Nilesh J. and McPherson, Ruth and Smith, George Davey and Frayling, Timothy M. and Wareham, Nicholas J. and Meigs, James B. and Mooser, Vincent and Spector, Tim D. (2009) A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels. PLOS GENETICS, 5 (12): e1000768. ISSN 1553-7404,
Full text not available from this repository. (Request a copy)Abstract
The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms ( SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P <= 5x10(-8)). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P <= 0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19) for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8), n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5610 26, n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3), n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MOLECULAR-WEIGHT ADIPONECTIN; BONE-MINERAL DENSITY; SMALL G-PROTEINS; INSULIN-RESISTANCE; PLASMA ADIPONECTIN; METABOLIC SYNDROME; CIRCULATING ADIPONECTIN; MYOCARDIAL-INFARCTION; SERUM CONCENTRATION; APM1 GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Aug 2020 12:36 |
| Last Modified: | 31 Aug 2020 12:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28089 |
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