NLRP3 Inflammasome Polymorphism and Macrovascular Complications in Type 2 Diabetes Patients.
BACKGROUND
It is generally accepted that poor glycemic control, arterial hypertension and/or hyperlipidemia, and the associated oxidative stress may contribute to the development of macro- and microvascular complications in type 2 diabetes (T2D). Such metabolic damage signals may activate inflammasome and trigger chronic inflammation. We investigated common polymorphisms in inflammasome coding genes and the risk for macro- and microvascular complications in T2D.


METHODS
In total 181 clinically well-characterised T2D patients were genotyped for NLRP3 rs35829419 and CARD8 rs2043211. Risk for diabetic complications was assessed using logistic regression.


RESULTS
Patients with median duration of T2D 11 (6-17) years had relatively well controlled blood glucose and lipid levels and blood pressure on the prescribed treatment regimen. Duration of T2D and plasma cholesterol levels were the most important clinical risk factors for macrovascular complications (P = 0.007 and P = 0.031). NLRP3 rs35829419 was associated with increased risk for macrovascular complications (P = 0.004), with myocardial infarction in particular (P = 0.052). No association was observed between CARD8 polymorphism and any of T2D complications.


CONCLUSIONS
Our preliminary data suggest the role of NLRP3 polymorphism in diabetic macrovascular complications, especially in myocardial infarction.
General Hospital Trbovlje, Rudarska cesta 9, SI-1420 Trbovlje, Slovenia.
Jasna
J
Klen
Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia.
Katja
K
Goričar
Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Zaloška Cesta 7, SI-1000 Ljubljana, Slovenia.
Andrej
A
Janež
Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia.
Vita
V
Dolžan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D002352:Carrier Proteins / Q000235:genetics*; D048909:Diabetes Complications / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D014652:Vascular Diseases / Q000150:complications* / Q000378:metabolism
D001786:Blood Glucose; D002352:Carrier Proteins; D058847:Inflammasomes; D008055:Lipids; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human