HbA1c-based diabetes diagnosis among patients with glucokinase mutation (GCK-MODY) is affected by a genetic variant of glucose-6-phosphatase (G6PC2)
HbA1c-based diabetes diagnosis among patients with glucokinase mutation (GCK-MODY) is affected by a genetic variant of glucose-6-phosphatase (G6PC2)
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DOI：
10.1111/j.1464-5491.2012.03671.x
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发表时间：
2012-11-01
影响因子：
3.5
通讯作者：
Mlynarski, W.
中科院分区：
文献类型：
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作者：
Borowiec, M.;Fendler, W.;Mlynarski, W.
已知葡萄糖 6 磷酸酶催化 2 基因 (G6PC2) rs560887 位点的遗传变异会影响空腹血糖的调节。我们确定了单基因糖尿病和葡萄糖激酶基因突变 (GCK-MODY) 患者的 rs560887 基因型，并将基因型与 HbA1c 水平相关联。方法 从波兰 (n = 128) 和捷克共和国 (n = 154) 的两个大型队列中招募来自 GCK-MODY 家族的患者。使用实时定量聚合酶链反应检查 G6PC2 中 rs560887 多态性位点的基因型。在两个队列中分别评估了 rs560887 基因型对 GCK-MODY 诊断时年龄和初始 HbA1c 水平的影响。随后，对波兰和捷克队列的 rs560887 基因型 HbA1c 关联进行了荟萃分析，以确认研究结果的同质性并验证特定队列的结果。结果 rs560887 的 GG 纯合性与 HbA1c 水平略微升高相关（两个队列中 P = 0.07）。两组中观察到的效果非常均匀（Q = 0.18；P = 0.68）。荟萃分析显示，rs560887 的 GG 纯合性与平均 HbA1c 水平相关，平均 HbA1c 水平比其他基因型个体高 2.4 mmol/mol (0.24%)，95% CI 0.54.4 mmol/mol (0.050.44%)。此外，对两个队列的荟萃分析表明，GG 纯合子个体达到 48 mmol/mol (6.5%) 糖尿病诊断阈值的几率更高； （比值比 1.90；95% CI 1.073.36；P = 0.03）。没有观察到糖尿病诊断时年龄的这种影响。结论 G6PC2 rs560887 位点的变异与 GCK 突变个体的糖化血红蛋白水平较差相关。 GG 纯合子更有可能符合基于 HbA1c 水平的糖尿病诊断标准。
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 genotypeHbA1c 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 0.54.4 mmol/mol (0.050.44%) 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 1.073.36; 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.