; Loos, Ruth J. F. ; Perry, John R. B. ; Tanaka, Toshiko
; Timpson, Nicholas John
; Semple, Robert K.
; Soranzo, Nicole ; Song, Kijoung ; Rocha, Nuno ; Grundberg, Elin
; Dupuis, Josée ; Florez, Jose C.
; Langenberg, Claudia
; Prokopenko, Inga ; Saxena, Richa
; Sladek, Robert
; Aulchenko, Yurii
; Evans, David ; Waeber, Gerard
; Erdmann, Jeanette ; Burnett, Mary-Susan ; Sattar, Naveed ; Devaney, Joseph
; Willenborg, Christina ; Hingorani, Aroon ; Witteman, Jaquelin C. M. ; Vollenweider, Peter ; Glaser, Beate ; Hengstenberg, Christian ; Ferrucci, Luigi
; Melzer, David
; Stark, Klaus ; Deanfield, John ; Winogradow, Janina ; Grassl, Martina
; Hall, Alistair S. ; Egan, Josephine M. ; Thompson, John R. ; Ricketts, Sally L. ; König, Inke R. ; Reinhard, Wibke ; Grundy, Scott ; Wichmann, H-Erich ; Barter, Phil ; Mahley, Robert ; Kesaniemi, Y. Antero ; Rader, Daniel J.
; Reilly, Muredach P. ; Epstein, Stephen E.
; Stewart, Alexandre F. R. ; Van Duijn, Cornelia M. ; Schunkert, Heribert ; Burling, Keith
; Deloukas, Panos ; Pastinen, Tomi ; Samani, Nilesh J. ; McPherson, Ruth ; Davey Smith, George ; Frayling, Timothy M. ; Wareham, Nicholas J. ; Meigs, James B. ; Mooser, Vincent ; Spector, Tim D. | Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | PLoS Genetics | ||||
| Verlag: | PUBLIC LIBRARY SCIENCE | ||||
| Ort der Veröffentlichung: | SAN FRANCISCO | ||||
| Band: | 5 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 12 | ||||
| Seitenbereich: | e1000768 | ||||
| Datum: | 2009 | ||||
| Institutionen: | Medizin > Lehrstuhl für Innere Medizin II | ||||
| Identifikationsnummer: |
| ||||
| Stichwörter / Keywords: | MOLECULAR-WEIGHT ADIPONECTIN; BONE-MINERAL DENSITY; SMALL G-PROTEINS; INSULIN-RESISTANCE; PLASMA ADIPONECTIN; METABOLIC SYNDROME; CIRCULATING ADIPONECTIN; MYOCARDIAL-INFARCTION; SERUM CONCENTRATION; APM1 GENE; | ||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 66744 |
Zusammenfassung
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 ...

Zusammenfassung
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.
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