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Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type
E Reiling1, E van 't Riet, M J Groenewoud
1Department of Molecular Cell Biology, Leiden University Medical Centre, PO Box 9600, 2300RC, Leiden, the Netherlands.
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.
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