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Polymorphisms in glyoxalase 1 gene are not associated with vascular complications: the Hoorn and CoDAM studies

Engelen, Liana,b; Ferreira, Isabelb,c; Brouwers, Olafa,b; Henry, Ronald MAa,b; Dekker, Jacqueline Md; Nijpels, Gield; Heine, Robert Jd; van Greevenbroek, Marleen MJa,b; van der Kallen, Carla JHa,b; Blaak, Ellen Ee,f; Feskens, Edith JMg; ten Cate, Hugoa,b; Stehouwer, Coen DAa,b; Schalkwijk, Casper Ga,b

doi: 10.1097/HJH.0b013e32832af6ba
Original papers: Genetic aspects
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Objectives Methylglyoxal is a major precursor in the formation of advanced glycation endproducts (AGEs), which are known to contribute to vascular complications such as hypertension and arterial stiffness. Methylglyoxal can be detoxified by glyoxalase 1 (GLO1). Because genetic variation in the GLO1 gene may alter the expression and/or the activity of GLO1, we investigated whether single nucleotide polymorphisms (SNPs) in the GLO1 gene are associated with vascular complications.

Methods The study entailed cross-sectional data analyses of the Cohort study of Diabetes and Atherosclerosis Maastricht (CoDAM) study and the Hoorn study, comprising a total of 1289 participants, aged 64.5 ± 8.58 years, of whom 43.5% had normal glucose metabolism, 23.2% had impaired glucose metabolism and 33.3% had type 2 diabetes mellitus. Nine tag SNPs that cover the common GLO1 gene variation were genotyped. Levels of blood pressure and markers of atherosclerosis, arterial stiffness, renal function and AGEs were compared across genotypes.

Results All genotyped SNPs were in Hardy–Weinberg equilibrium. Prevalence of hypertension and markers of atherosclerosis, arterial stiffness, renal function and AGEs did not differ across genotypes of the nine SNPs. In additive models, SNP18 (rs2736654) was associated with pulse pressure [−1.20 mmHg (95% confidence interval: −2.26;−0.14)] and SNP40 (rs10484854) was associated with systolic blood pressure [−1.77 mmHg (−3.40;−0.14)].

Conclusion Polymorphisms in the GLO1 gene are not associated with the prevalence of hypertension, markers of atherosclerosis, renal function and AGEs and are weakly associated with pulse pressure and systolic blood pressure (possibly due to chance) in two Dutch cohorts of patients with normal glucose metabolism, impaired glucose metabolism and type 2 diabetes mellitus.

aCardiovascular Research Institute Maastricht (CARIM), The Netherlands

bDepartment of Internal Medicine, The Netherlands

cDepartment of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Centre, Maastricht, The Netherlands

dInstitute for Research in Extramural Medicine (EMGO), VU Medical Center, Amsterdam, The Netherlands

eDepartment of Human Biology, The Netherlands

fNutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University Medical Centre, Maastricht, The Netherlands

gDivision of Human Nutrition, Wageningen University, Wageningen, The Netherlands

Received 16 February, 2009

Accepted 26 February, 2009

Correspondence to Casper G. Schalkwijk, Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Centre, Debeyelaan 25, PO Box 5800, 6202 AZ Maastricht, The Netherlands Tel: +31 43 3882186; fax: +31 43 3875006; e-mail: C.Schalkwijk@intmed.unimaas.nl

© 2009 Lippincott Williams & Wilkins, Inc.