Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk - PubMed (original) (raw)
Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk
E Reiling et al. Diabetologia. 2009 Sep.
Abstract
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 <or= 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 x 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 x 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 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.
Figures
Fig. 1
Combined effect of GCK, GCKR, G6PC2 and MTNR1B on FPG and HbA1c in non-diabetic participants from the New Hoorn Study. a Fasting plasma glucose. Numbers within the bars are numbers of participants per allele group. The per allele effect was 0.05 (0.04–0.07) mmol/l, p = 2 × 10−13). Error bars represent 95% CI. b HbA1c. Numbers within the bars represent the number of participants per allele group. The per allele effect was 0.03% (0.02–0.04%), p = 5 × 10−10 Error bars represent 95% CI
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References
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1007/s001250051249', 'is_inner': False, 'url': 'https://doi.org/10.1007/s001250051249'}, {'type': 'PubMed', 'value': '10491751', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/10491751/'}\]}
- de Vegt F, Dekker JM, Ruhe HG et al (1999) Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia 42:926–931 - PubMed
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1001/jama.285.16.2109', 'is_inner': False, 'url': 'https://doi.org/10.1001/jama.285.16.2109'}, {'type': 'PubMed', 'value': '11311100', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/11311100/'}\]}
- de Vegt F, Dekker JM, Jager A et al (2001) Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: The Hoorn Study. JAMA 285:2109–2113 - PubMed
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1002/(SICI)1098-2272(1999)16:4<426::AID-GEPI8>3.0.CO;2-B', 'is_inner': False, 'url': 'https://doi.org/10.1002/(sici)1098-2272(1999)16:4<426::aid-gepi8>3.0.co;2-b'}, {'type': 'PubMed', 'value': '10207722', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/10207722/'}\]}
- Snieder H, Boomsma DI, van Doornen LJ, Neale MC (1999) Bivariate genetic analysis of fasting insulin and glucose levels. Genet Epidemiol 16:426–446 - PubMed
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.2337/diabetes.54.2.576', 'is_inner': False, 'url': 'https://doi.org/10.2337/diabetes.54.2.576'}, {'type': 'PubMed', 'value': '15677518', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/15677518/'}\]}
- Weedon MN, Frayling TM, Shields B et al (2005) Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene. Diabetes 54:576–581 - PubMed
- {'text': '', 'ref_index': 1, 'ids': [{'type': 'DOI', 'value': '10.1126/science.1142358', 'is_inner': False, 'url': 'https://doi.org/10.1126/science.1142358'}, {'type': 'PubMed', 'value': '17463246', 'is_inner': True, 'url': 'http://pubmed.ncbi.nlm.nih.gov/17463246/'}\]}
- The Diabetes Genetics Initiative of the Broad Institute of MIT and Harvard and Lund University and Novartis Institutes for BioMedical Research (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336 - PubMed
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