Angiotensin-converting enzyme genotype, albuminuria and plasma fibrinogen in type 2 diabetes mellitus.
OBJECTIVE
Increased fibrinogen level is considered an important atherosclerosis risk factor. Patients with type 2 diabetes frequently have increased fibrinogen levels. The aim of the present study was to examine the effect of angiotensin-converting enzyme (ACE) gene polymorphism and the effects of the diabetic environment on plasma fibrinogen in type 2 diabetes.


METHODS
The study group included 125 patients with type 2 diabetes (40 men, 85 women). The average age of patients was 62 +/- 10 years. Fibrinogen concentration was determined with the thrombin coagulation test. ACE insertion/deletion (I/D) polymorphism was detected using polymerase chain reaction (PCR) assay.


RESULTS
II homozygotes (n = 17) had the highest mean fibrinogen levels, ID heterozygotes (n = 75) had medium levels and DD homozygotes (n = 33) had the lowest (p = 0.054, ANOVA). II homozygotes also had significantly higher mean fibrinogen level than ID/DD carriers (4.3 +/- 1.7 vs. 3.5 +/- 1.3 g/l; p = 0.015). The indices of renal functions, i.e. albuminuria (r = 0.37; p < 0.0001) and serum creatinine (r = 0.22; p = 0.015), significantly correlated with fibrinogen levels. The correlation between albuminuria and fibrinogen was significant in the subgroups with genotypes II (r = 0.76; p = 0.001) and ID (r = 0.37, p = 0.002), whereas in the subgroup of DD homozygotes this relationship did not reach statistical significance. In the multivariate regression analysis with age, sex, BMI, creatinine, albuminuria and ACE genotype as independent variables, albuminuria was the only significant predictor of fibrinogen level (p < 0.0001). After interaction between the ACE genotype and albuminuria was included into multivariate analysis, the interaction became the only independent predictor of plasma fibrinogen level (p < 0.0001) in the model, and the model explained 25% of the plasma fibrinogen variance.


CONCLUSIONS
ACE gene polymorphism is associated with plasma fibrinogen level in type 2 diabetes. This association is mediated by an interaction between ACE genotype and albuminuria. Diabetes patients with genotypes II or ID have increased plasma fibrinogen in the presence of albuminuria.
Tkác
Ivan
I
Department of Internal Medicine 4, Faculty of Medicine, P. J. Safárik University, Kosice, Slovakia. IvanTkac@medic.upjs.sk
Salagovic
Ján
J
Kozárová
Miriam
M
Javorský
Martin
M
Tkácová
Ruzena
R
Kalina
Ivan
I
D000368:Aged; D000419:Albuminuria / Q000209:etiology*; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000652:urine; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020913:Perindopril / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D005340:Fibrinogen; D006442:Glycated Hemoglobin; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril