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HbA1c‐based diabetes diagnosis among patients with glucokinase mutation (GCK‐MODY) is affected by a genetic variant of glucose‐6‐phosphatase (G6PC2)
Author(s) -
Borowiec M.,
Fendler W.,
Dusatkova P.,
Antosik K.,
Pruhova S.,
Cinek O.,
Mysliwiec M.,
JaroszChobot P.,
Malecki M. T.,
Mlynarski W.
Publication year - 2012
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2012.03671.x
Subject(s) - glucokinase , medicine , genotype , diabetes mellitus , odds ratio , endocrinology , genetics , biology , gene
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 HbA 1c 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 HbA 1c levels were evaluated separately within both cohorts. Following that, a meta‐analysis of rs560887 genotype–HbA 1c 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 HbA 1c 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 HbA 1c 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 HbA 1c level.