The association of myeloperoxidase promoter polymorphism with carotid atherosclerosis is abolished in patients with type 2 diabetes.
OBJECTIVE
Type 2 diabetes mellitus (DM) enhances the development of atherosclerosis and reduces the activity of the oxidative myeloperoxidase (MPO) enzyme. MPO gene has a functional promoter polymorphism -463G/A which leads to high- (GG) and low-expression (AG, AA) genotypes.


METHODS
We studied the association of MPO polymorphism with carotid artery intima-media thickness (IMT) in 198 randomly selected Finnish men of Caucasian origin, 161 non-diabetics and 37 with type 2 DM. Their carotid IMT was measured by high-resolution ultrasonography, and the overall mean IMT value was calculated. MPO genotypes were determined by the PCR-RFLP method.


RESULTS
We found significant MPO genotype-by-study-group (control/DM) interactions with the overall mean IMT and internal carotid IMT (p=0.05 and p=0.04, respectively). Among non-diabetic subjects, the overall carotid IMT was 7.3% higher in subjects with the low-activity genotype when compared to the high-activity (G/G) group. The results remained significant after adjustment for total cholesterol and smoking (p=0.015). No similar genotypic association was found for the subjects with type 2 DM.


CONCLUSIONS
This data suggests that in subjects with normal glucose metabolism, MPO gene variation may modify the carotid artery IMT.
Mäkelä
Riikka
R
Tampere University Hospital, Centre for Laboratory Medicine, Department of Clinical Chemistry, Tampere, Finland. riikka.makela@uta.fi
Loimaala
Antti
A
Nenonen
Arja
A
Mercuri
Michele
M
Vuori
Ilkka
I
Huhtala
Heini
H
Oja
Pekka
P
Bond
Gene
G
Koivula
Timo
T
Lehtimäki
Terho
T
D001786:Blood Glucose / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D001786:Blood Glucose; D009195:Peroxidase