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

Abstract

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.

Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients

“…Moreover, FN3K SNPs associated significantly with typical aspects of diabetes have been described [28][29][30]. All this evidence reinforces the hypothesis that the combination of particular variants in the promoter and exon regions could turn into enhanced or reduced expression of other enzymes or regulator factors involved into deglycation.…”

“…However, they failed to detect a correlation between FN3K SNPs and HbA 1c levels [27]. Then, the group of Mohás analyzed a large cohort of type 2 diabetic (T2DM) subjects (859 T2DM and 265 controls) for the presence of the polymorphism c.900C/G (rs1056534) of the FN3K gene [28]. They found that the C allele of rs1056534 was coupled with lower HbA 1c concentration and with a later onset of type 2 diabetes.…”

Genetic variability in enzymes of metabolic pathways conferring protection against non-enzymatic glycation versus diabetes-related morbidity and mortality

“…Of those we found marginal association of rs1056534 located in exon 6 with DN progression. This SNP was previously associated with HbA1C and onset of diabetes, but not with any type of diabetic microvascular complications [15]. The most thorough analysis was performed for genetic variation in TKT, an important enzyme of the non-oxidative branch of PPP with proven increase of activity in diabetes [5].…”

Association of Glycation Gap With Mortality and Vascular Complications in Diabetes

“…Protein glycation is a nonenzymatic reaction dependent on glucose concentrations, but intracellular enzymatic deglycation of proteins has also been identified (10). The key deglycating enzyme, fructosamine-3-kinase, has isoforms and a genetic polymorphism suggested to influence HbA 1c variability, but any impact on HbA 1c glycation is unknown; although it seems unlikely that glycated HbA 1c is a substrate for this enzyme since it has been shown that there is no evidence that it plays any role in HbA 1c deglycation at the relevant glycation site (11,12). To add to the potential for a spurious generation of a G-gap, many factors, including variability in protein turnover and obesity, may affect fructosamine estimation (1,13,14).…”