Variability in erythrocyte fructosamine 3-kinase activity in humans correlates with polymorphisms in the FN3K gene and impacts on haemoglobin glycation at specific sites.
BACKGROUND
Part of the fructosamines that are bound to intracellular proteins are repaired by fructosamine 3-kinase (FN3K). Because subject-to-subject variations in erythrocyte FN3K activity could affect the level of glycated haemoglobin independently of differences in blood glucose level, we explored if such variability existed, if it was genetically determined by the FN3K locus on 17q25 and if the FN3K activity correlated inversely with the level of glycated haemoglobin.


RESULTS
The mean erythrocyte FN3K activity did not differ between normoglycaemic subjects (n = 26) and type 1 diabetic patients (n = 31), but there was a wide interindividual variability in both groups (from about 1 to 4 mU/g haemoglobin). This variability was stable with time and associated (P < 0.0001) with two single nucleotide polymorphisms in the promoter region and exon 6 of the FN3K gene. There was no significant correlation between FN3K activity and the levels of HbA1c, total glycated haemoglobin (GHb) and haemoglobin fructoselysine residues, either in the normoglycaemic or diabetic group. However, detailed analysis of the glycation level at various sites in haemoglobin indicated that the glycation level of Lys-B-144 was about twice as high in normoglycaemic subjects with the lowest FN3K activities as compared to those with the highest FN3K activities.


CONCLUSIONS
Interindividual variability of FN3K activity is substantial and impacts on the glycation level at specific sites of haemoglobin, but does not detectably affect the level of HbA1c or GHb. As FN3K opposes one of the chemical effects of hyperglycaemia, it would be of interest to test whether hypoactivity of this enzyme favours the development of diabetic complications.
Delpierre
G
G
Laboratory of Physiological Chemistry, ICP and Université catholique de Louvain, Brussels, Belgium.
Veiga-da-Cunha
M
M
Vertommen
D
D
Buysschaert
M
M
Van Schaftingen
E
E
D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values
D017931:DNA Primers; D006442:Glycated Hemoglobin; D008239:Lysine; D017853:Phosphotransferases (Alcohol Group Acceptor); C033186:fructosyl-lysine; C414347:fructosamine-3-kinase