Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk.

Autor: Reiling E; Department of Molecular Cell Biology, Leiden University Medical Centre, PO Box 9600, 2300RC, Leiden, the Netherlands., van 't Riet E, Groenewoud MJ, Welschen LM, van Hove EC, Nijpels G, Maassen JA, Dekker JM, 't Hart LM
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2009 Sep; Vol. 52 (9), pp. 1866-70. Date of Electronic Publication: 2009 Jun 17.
DOI: 10.1007/s00125-009-1413-9
Abstrakt: Aims/hypothesis: Variation in fasting plasma glucose (FPG) within the normal range is a known risk factor for the development of type 2 diabetes. Several reports have shown that genetic variation in the genes for glucokinase (GCK), glucokinase regulatory protein (GCKR), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2) and melatonin receptor type 1B (MTNR1B) is associated with FPG. In this study we examined whether these loci also contribute to type 2 diabetes susceptibility.
Methods: A random selection from the Dutch New Hoorn Study was used for replication of the association with FGP (2,361 non-diabetic participants). For the genetic association study we extended the study sample with 2,628 participants with type 2 diabetes. Risk allele counting was used to calculate a four-gene risk allele score for each individual.
Results: Variants of the GCK, G6PC2 and MTNR1B genes but not GCKR were associated with FPG (all, p Conclusions: A combined risk allele score for single-nucleotide polymorphisms in four known FPG loci is significantly associated with FPG and HbA(1c) in a Dutch population-based sample of non-diabetic participants. Carriers of low or high numbers of risk alleles show significantly different risks for type 2 diabetes compared with the reference group.
Databáze: MEDLINE
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