A polymorphism within the fructosamine-3-kinase gene is associated with HbA1c 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.

• Authors: M Mohás, P Kisfali, E Baricza, A Mérei, A Maász, J Cseh, E Mikolás, I A Szijártó, B Melegh, I Wittmann
• Journal: Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association (Exp Clin Endocrinol Diabetes) Vol. 118 Issue 3 Pg. 209-12 (Mar 2010) ISSN: 1439-3646 [Electronic] Germany
• PMID: 19834870 (Publication Type: Journal Article)
• Copyright: J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart * New York.

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• hemoglobin A1c protein, human
• Phosphotransferases (Alcohol Group Acceptor)
• fructosamine-3-kinase

Topics

• Age of Onset
• Blood Glucose (analysis)
• Body Mass Index
• Diabetes Mellitus, Type 2 (complications, genetics)
• Diabetic Angiopathies (enzymology, genetics)
• Female
• Genetic Association Studies
• Glycated Hemoglobin (analysis, metabolism)
• Humans
• Male
• Middle Aged
• Phosphotransferases (Alcohol Group Acceptor) (genetics)
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide