Glyoxalase 1 enzyme activity in erythrocytes and Ala111Glu polymorphism in type 1-diabetes patients.
OBJECTIVE
The enzyme glyoxalase 1 (GLO1) can inactivate the glycoxidation product methylglyoxal that is thought to be an important contributor to the pathogenesis of vascular complications in diabetes. We aimed to study erythrocyte GLO1 activity and whether the Ala111Glu GLO1 gene polymorphism affected GLO1 activity.


METHODS
Fasting erythrocyte GLO1 activity was measured spectrophotometrically. The A111G gene polymorphism, assessed in DNA from leucocytes was analyzed in patients with type 1-diabetes and normal kidney function and compared with a control group.


RESULTS
Sixty-one patients with type 1-diabetes duration of 26.1 (10.7) years, mean (SD) with a HbA1c of 7.8 (0.9)%, 61.7 (9.9) mmol/mol and normal glomerular filtration rate were compared with 62 age- and sex-matched healthy controls. GLO1 activity was 0.206 (0.183-0.231) median (25-75% percentiles) U/mg Hb in the control group vs. 0.192 (0.165-0.224) in the diabetes group, (p = 0.149). In the diabetes group GLO1 correlated with HbA1c (r = 0.33, p < 0.01) and oxidized glutathione (GSSG) (r = - 0.34, p < 0.01) and in the control group with GSH (r = 0.37, p < 0.005) and fasting glucose (r = 0.26, p < 0.04). In a multiple regression analysis with GLO1 activity as the dependent variable, including the Ala111Glu polymorphism, the significant independent variables were log GSSG (ß - 0.318, p = 0.02) and HbA1c (ß 0.285, p = 0.041) in the diabetes group and log GSH, (ß 0.407, p = 0.004) in the control group.


CONCLUSIONS
Erythrocyte glyoxalase 1 activity did not differ between patients with type 1-diabetes and controls. The Ala111Glu glyoxalase gene polymorphism did not have an effect on glyoxalase 1 activity in either group.
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway.
Amrit K
AK
Sakhi
Jens P
JP
Berg
Tore J
TJ
Berg
D000328:Adult; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000235:genetics; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D006442:Glycated Hemoglobin; D007791:Lactoylglutathione Lyase; C517652:hemoglobin A1c protein, human