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New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk


Dupuis, Josee; Langenberg, Claudia; Prokopenko, Inga; Saxena, Richa; Soranzo, Nicole; The MAGIC Consortium (270 co-authors); Polašek, Ozren; Rudan, Igor; McCarthy, Mark I.; Florez, Jose C.; Barroso, Ines ...
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk // Nature genetics, 42 (2010), 2; 105-116 doi::10.1038/ng.520 (međunarodna recenzija, članak, znanstveni)


Naslov
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Autori
Dupuis, Josee ; Langenberg, Claudia ; Prokopenko, Inga ; Saxena, Richa ; Soranzo, Nicole ; The MAGIC Consortium (270 co-authors) ; Polašek, Ozren ; Rudan, Igor ; McCarthy, Mark I. ; Florez, Jose C. ; Barroso, Ines ...

Izvornik
Nature genetics (1061-4036) 42 (2010), 2; 105-116

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Genome wide association study; glucose; diabetes type 2

Sažetak
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46, 186 nondiabetic participants. Follow-up of 25 loci in up to 76, 558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Javno zdravstvo i zdravstvena zaštita



POVEZANOST RADA


Projekt / tema
216-1080315-0302 - Odrednice zdravlja i bolesti u općoj i izoliranim ljudskim populacijama (Ozren Polašek, )

Ustanove
Medicinski fakultet, Zagreb,
Medicinski fakultet, Split

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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