A polymorphism within the fructosamine-3-kinase gene is associated with HbA1c Levels and the onset of type 2 diabetes mellitus

Exp Clin Endocrinol Diabetes. 2010 Mar;118(3):209-12. doi: 10.1055/s-0029-1238319. Epub 2009 Oct 15.

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.

MeSH terms

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

Substances

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