Role of fructosamine-3-kinase in protecting against the onset of microvascular and macrovascular complications in patients with T2DM

Abstract

Introduction: Microangiopathic and macroangiopathic complications are the main cause of morbidity and mortality in the diabetic population. Numerous publications have highlighted the role of glycation in the onset of complications of diabetes. In this context, the detection of fructosamine-3-kinase (FN3K)-an enzyme capable of counteracting the effect of hyperglycemia by intervening in protein glycation-has attracted great interest. Several studies have linked FN3K genetic variability to its enzymatic activity and glycated hemoglobin (HbA1c) levels. Here, we investigated the role of FN3K polymorphisms in the development of microvascular and macrovascular complications of diabetes.

Research design and methods: The anthropometric and biochemical parameters, and any medical history of microangiopathic and macroangiopathic complications, were documented in a sample of 80 subjects with type 2 diabetes. All subjects were screened for FN3K gene and analyzed for the combination of three polymorphisms known to be associated with its enzymatic activity (rs3859206 and rs2256339 in the promoter region and rs1056534 in exon 6).

Results: The combination of allelic variants of FN3K polymorphisms resulted in 13 distinct genotypic variants within the cohort. Comparison between genotypes showed no significant differences in terms of demographic, anthropometric and biochemical parameters, risk markers and long-term complications, except for a higher age and vitamin E levels associated with the genotype presenting GG at position -385, TT at position -232, and CC at c.900 A. Evaluating the microangiopathic and macroangiopathic complications as a whole, we found that they appeared significantly less present in this genotype compared with all other genotypes (p=0.0306).

Conclusions: The group of patients carrying the favorable allele for the three polymorphisms of the FN3K gene revealed less severe microangiopathy and macroangiopathy, suggesting a protective role of this genotype against the onset of the complications of diabetes.

Keywords: diabetes mellitus, type 2; fructosamine-3-kinase; genetic polymorphisms; vasculopathy.

Figure 1

Box plot showing the distribution of the combined microangiopathic and macroangiopathic complications in the FN3K genotype groups. The total number of complications per patient includes the presence of at least one of the following: cerebral macroangiopathy, peripheral artery disease, ischemic heart disease, retinopathy, and microalbuminuria. The Kruskal-Wallis test indicated a statistically significant difference among the genotype groups (p=0.0306). **p<0.01, *p<0.05 post hoc analysis versus genotype group A. In the graph, the edges of the box indicate the 25th and 75th quantiles, including the middle 50% of the data; whiskers indicate the range of data, calculated as [upper quartile+1.5 (IQR)] and [lower quartile−1.5 (IQR)]; the continuous horizontal line is the overall arithmetical mean for all the data; the scattered points are single subject’s values. The width of each box is proportional to the number of cases in each group. FN3K, fructosamine-3-kinase.