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

Abstract

IntroductionMicroangiopathic 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 linkedFN3Kgenetic variability to its enzymatic activity and glycated hemoglobin (HbA1c) levels. Here, we investigated the role ofFN3Kpolymorphisms in the development of microvascular and macrovascular complications of diabetes.Research design and methodsThe 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 forFN3Kgene 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).ResultsThe combination of allelic variants ofFN3Kpolymorphisms 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).ConclusionsThe group of patients carrying the favorable allele for the three polymorphisms of theFN3Kgene revealed less severe microangiopathy and macroangiopathy, suggesting a protective role of this genotype against the onset of the complications of diabetes.