TY - JOUR
T1 - Polymorphisms in Glyoxalase I Gene Are Not Associated with Glyoxalase I Expression in Whole Blood or Markers of Methylglyoxal Stress: The CODAM Study
AU - Maasen, K.
AU - Hanssen, N.M.J.
AU - van der Kallen, C.J.H.
AU - Stehouwer, C.D.A.
AU - van Greevenbroek, M.M.J.
AU - Schalkwijk, C.G.
N1 - Funding Information:
Funding: This research was funded by the Office of Risk Assessment and Research of the Netherlands Food and Consumer Product Safety Authority (NVWA). The initiation of CODAM was supported by grants of the Netherlands Organisation for Scientific Research (940-35-034) and the Dutch Diabetes Research Foundation (98.901). The APC were covered by Maastricht University.
Funding Information:
This research was funded by the Office of Risk Assessment and Research of the Netherlands Food and Consumer Product Safety Authority (NVWA). The initiation of CODAM was supported by grants of the Netherlands Organisation for Scientific Research (940-35-034) and the Dutch Diabetes Research Foundation (98.901). The APC were covered by Maastricht University.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Glyoxalase 1 (Glo1) is the rate-limiting enzyme in the detoxification of methylglyoxal (MGO) into D-lactate. MGO is a major precursor of advanced glycation endproducts (AGEs), and both are associated with development of age-related diseases. Since genetic variation in GLO1 may alter the expression and/or the activity of Glo1, we examined the association of nine SNPs in GLO1 with Glo1 expression and markers of MGO stress (MGO in fasting plasma and after an oral glucose tolerance test, D-lactate in fasting plasma and urine, and MGO-derived AGEs CEL and MG-H1 in fasting plasma and urine). We used data of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM, n = 546, 60 +/- 7 y, 25% type 2 diabetes). Outcomes were compared across genotypes using linear regression, adjusted for age, sex, and glucose metabolism status. We found that SNP4 (rs13199033) was associated with Glo1 expression (AA as reference, standardized beta AT = -0.29, p = 0.02 and TT = -0.39, p = 0.3). Similarly, SNP13 (rs3799703) was associated with Glo1 expression (GG as reference, standardized beta AG = 0.17, p = 0.14 and AA = 0.36, p = 0.005). After correction for multiple testing these associations were not significant. For the other SNPs, we observed no consistent associations over the different genotypes. Thus, polymorphisms of GLO1 were not associated with Glo1 expression or markers of MGO stress, suggesting that these SNPs are not functional, although activity/expression might be altered in other tissues.
AB - Glyoxalase 1 (Glo1) is the rate-limiting enzyme in the detoxification of methylglyoxal (MGO) into D-lactate. MGO is a major precursor of advanced glycation endproducts (AGEs), and both are associated with development of age-related diseases. Since genetic variation in GLO1 may alter the expression and/or the activity of Glo1, we examined the association of nine SNPs in GLO1 with Glo1 expression and markers of MGO stress (MGO in fasting plasma and after an oral glucose tolerance test, D-lactate in fasting plasma and urine, and MGO-derived AGEs CEL and MG-H1 in fasting plasma and urine). We used data of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM, n = 546, 60 +/- 7 y, 25% type 2 diabetes). Outcomes were compared across genotypes using linear regression, adjusted for age, sex, and glucose metabolism status. We found that SNP4 (rs13199033) was associated with Glo1 expression (AA as reference, standardized beta AT = -0.29, p = 0.02 and TT = -0.39, p = 0.3). Similarly, SNP13 (rs3799703) was associated with Glo1 expression (GG as reference, standardized beta AG = 0.17, p = 0.14 and AA = 0.36, p = 0.005). After correction for multiple testing these associations were not significant. For the other SNPs, we observed no consistent associations over the different genotypes. Thus, polymorphisms of GLO1 were not associated with Glo1 expression or markers of MGO stress, suggesting that these SNPs are not functional, although activity/expression might be altered in other tissues.
KW - advanced glycation endproducts
KW - codam
KW - d-lactate
KW - gene expression
KW - glyoxalase 1
KW - glyoxalase pathway
KW - methylglyoxal
KW - mrna
KW - single nucleotide polymorphism
KW - D-lactate
KW - CODAM
KW - mRNA
U2 - 10.3390/antiox10020219
DO - 10.3390/antiox10020219
M3 - Article
C2 - 33540757
SN - 2076-3921
VL - 10
JO - Antioxidants
JF - Antioxidants
IS - 2
M1 - 219
ER -