Elsevier

Diabetes & Metabolism

Volume 32, Issue 1, February 2006, Pages 31-39
Diabetes & Metabolism

Original article
Variability in erythrocyte fructosamine 3-kinase activity in humans correlates with polymorphisms in the FN3K gene and impacts on haemoglobin glycation at specific sites

https://doi.org/10.1016/S1262-3636(07)70244-6Get rights and content

Summary

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 nucle-otide 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-β-144 was about twice as high in normoglycaemic subjects with the lowest FN3K activities as compared to those with the highest FN3K activities.

Conclusion

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.

Résumé

La variabilité de l'activité fructosamine-3-kinase dans les érythrocytes humains corrèle avec des polymorphismes du gène FN3K et détermine le niveau de glycation de sites spécifiques de l'hémoglobine

Contexte

La fructosamine-3-kinase (FN3K) débarrasse les protéines intracellulaires d'une partie de leurs résidus fructosamines. Puisque des variations inter-individuelles de l'activité FN3K dans les érythrocytes pourraient affecter le niveau d'hémoglobine glyquée indépendamment de la concentration en glucose, notre objectif était de vérifier si de telles variations existent et, le cas échéant, si elles sont déterminées par le locus FN3K en 17q25 et si l'activité FN3K est en corrélation inverse avec le niveau d'hémoglobine glyquée.

Résultats

Il n'y avait pas de différence entre les activités FN3K moyennes mesurées dans les érythrocytes de sujets normoglycémi-ques (n = 26) ou de diabétiques de type 1 (n = 31), mais bien une large variabilité inter-individuelle, et ce dans les deux groupes (d'environ 1 à 4 mU/g d'hémoglobine). Cette variabilité était stable et associée (P < 0,0001) à deux polymorphismes situés dans la région promotrice et l'exon 6 du gène FN3K. L'activité FN3K n'était en corrélation de façon significative ni avec le taux d'HbA1c, ni avec ceux d'hémoglobine glyquée totale (HbG) et des résidus fructoselysine liés à l'hémoglobine, que ce soit dans le groupe normoglycémique ou diabétique. Toutefois, une analyse détaillée du niveau de glycation de différents sites de l'hémoglobine a révélé que dans le cas de la Lys-β-144, ce niveau était environ deux fois plus élevé chez les sujets normoglycémiques aux activités FN3K les plus basses, que chez ceux qui possédaient les activités FN3K les plus élevées. Conclusion: La variabilité inter-individuelle de l'activité FN3K est substantielle et affecte le niveau de glycation de sites spécifiques de l'hémoglobine, sans toutefois affecter de façon détectable les taux d'HbA1c et HbG. La FN3K contrecarrant un des effets chimiques de l'hyperglycémie, il serait intéressant de déterminer si une hypoacti-vité de cette enzyme favorise le développement des complications du diabète.

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