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

Autor: E. C. van Hove, Marlous J. Groenewoud, E. van 't Riet, Johannes A Maassen, L.M.C. Welschen, Erwin Reiling, Leen M 't Hart, J. M. Dekker, Giel Nijpels
Přispěvatelé: General practice, Internal medicine, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes
Rok vydání: 2009
Předmět:
Zdroj: Diabetologia, 52(9), 1866-1870. Springer Verlag
Diabetologia
Reiling, E, van 't Riet, E, Groenewoud, M J, Welschen, L M C, van Hove, E C, Nijpels, M G A A M, Maassen, J A, Dekker, J M & Hart, L M 2009, ' Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk ', Diabetologia, vol. 52, no. 9, pp. 1866-1870 . https://doi.org/10.1007/s00125-009-1413-9
ISSN: 0012-186X
DOI: 10.1007/s00125-009-1413-9
Popis: 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 ≤ 0.001; GCKR, p = 0.23). Combining these four genes in a risk allele score resulted in an increase of 0.05 mmol/l (0.04–0.07) per additional risk allele (p = 2 × 10−13). Furthermore, participants with less than three or more than five risk alleles showed significantly different type 2 diabetes susceptibility compared with the most common group with four risk alleles (OR 0.77 [0.65–0.93], p = 0.005 and OR 2.05 [1.50–2.80], p = 4 × 10−6 respectively). The age at diagnosis was also significantly associated with the number of risk alleles (p = 0.009). Conclusions A combined risk allele score for single-nucleotide polymorphisms in four known FPG loci is significantly associated with FPG and HbA1c 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. Electronic supplementary material The online version of this article (doi:10.1007/s00125-009-1413-9) contains supplementary material, which is available to authorised users.
Databáze: OpenAIRE
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