These authors contributed equally to this study.
Short Report: Genetics
HbA1c-based diabetes diagnosis among patients with glucokinase mutation (GCK-MODY) is affected by a genetic variant of glucose-6-phosphatase (G6PC2)
Article first published online: 7 OCT 2012
© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK
Volume 29, Issue 11, pages 1465–1469, November 2012
How to Cite
Borowiec, M., Fendler, W., Dusatkova, P., Antosik, K., Pruhova, S., Cinek, O., Mysliwiec, M., Jarosz-Chobot, P., Malecki, M. T. and Mlynarski, W. (2012), HbA1c-based diabetes diagnosis among patients with glucokinase mutation (GCK-MODY) is affected by a genetic variant of glucose-6-phosphatase (G6PC2). Diabetic Medicine, 29: 1465–1469. doi: 10.1111/j.1464-5491.2012.03671.x
- Issue published online: 7 OCT 2012
- Article first published online: 7 OCT 2012
- Accepted manuscript online: 4 APR 2012 12:42PM EST
- Accepted 30 March 2012
Aims Genetic variation at the rs560887 locus of the glucose-6-phosphatase, catalytic 2 gene (G6PC2) is known to affect regulation of fasting glycaemia. We determined the rs560887 genotype of patients with monogenic diabetes and glucokinase gene mutations (GCK-MODY) and correlated the genotypes with HbA1c levels.
Methods Patients from families with GCK-MODY were recruited from two large cohorts from Poland (n = 128) and the Czech Republic (n = 154). Genotypes at the rs560887 polymorphic site in G6PC2 were examined using real-time quantitative polymerase chain reaction. The effect of rs560887 genotype on age at diagnosis of GCK-MODY and initial HbA1c levels were evaluated separately within both cohorts. Following that, a meta-analysis of rs560887 genotype–HbA1c associations of both Polish and Czech cohorts was performed to confirm homogeneity of findings and validate cohort-specific results.
Results GG homozygosity at rs560887 was associated with marginally elevated HbA1c levels (P = 0.07 in both cohorts). The effects observed in both groups were very homogeneous (Q = 0.18; P = 0.68). Meta-analysis showed that GG homozygosity at rs560887 was associated with mean HbA1c levels higher by 2.4 mmol/mol (0.24%), 95% CI 0.5–4.4 mmol/mol (0.05–0.44%) than in individuals with other genotypes. Additionally, meta-analysis of both cohorts showed that GG homozygous individuals had higher odds of reaching the 48 mmol/mol (6.5%) diagnostic threshold of diabetes; (odds ratio 1.90; 95% CI 1.07–3.36; P = 0.03). No such effects were observed for age at diagnosis of diabetes.
Conclusions Variation at the rs560887 locus of G6PC2 is associated with worse glycated haemoglobin levels in individuals with GCK mutations; GG homozygotes are more likely to meet diagnostic criteria for diabetes based on HbA1c level.