A Polymorphism within the Fructosamine-3-kinase Gene is Associated with HbA_1c Levels and the Onset of Type 2 Diabetes Mellitus

Abstract

Background: Non-enzymatic glycation is a process, which leads to the formation of advanced glycation endproducts. These compounds are involved in the development of diabetic microvascular complications. Fructosamine-3-kinase (FN3K) is an intracellular enzyme that phosphorylates fructosamines resulting in fructosamine-3-phosphate, which subsequently decomposes to inorganic phosphate, 3-deoxyglucasone and the unmodified amine. Recently, the G900C (rs1056534) single nucleotide polymorpism (SNP) of the FN3K gene was found to be associated with the enzyme activity.

Objective/Design: The aim of the study was to investigate the impact of the SNP on clinical and biochemical features and microvascular complications of type 2 diabetes.

Patients: A total of 859 type 2 diabetic subjects and 265 healthy controls were enrolled in the study and were genotyped with PCR-RFLP method.

Results: Genotype frequencies were as follows, CC: 5%, GC: 54%, GG: 41% in subjects with type 2 diabetes and CC: 6%, GC: 51%, GG: 43% in the controls. Diabetic subjects with the CC variant had lower HbA_1c levels compared with the others (CC: 6.48±0.05%; GC: 7.66±0.09%; GG: 7.68±0.09%; p<0.001). Furthermore, in case of the CC allelic variant type 2 diabetes was diagnosed at a later age than in case of GC or GG variants (CC: 56.0±1.90 years; GC: 52.0±0.62 years; GG: 50.1±0.71 years; p<0.05). Logistic regression analysis did not reveal association between CC genotype and diabetic complications, such as diabetic nephropathy, neuropathy and retinopathy (OR=1.036, CI 95% 0.652–1.647, p=0.880; OR=0.985, CI 95% 0.564–1.721 p=0.958; OR=1.213, CI 95% 0.470–3.132, p=0.690, respectively).

Conclusion: We conclude that the G900C polymorphism associates with the level of HbA_1c and the onset of the disease, but not with either of the diabetic microvascular complications.

Key words

fructosamine-3-kinase - single nucleotide polymorphism - HbA_1c - diabetic microvascular complication

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