The effect of Toll-like receptor 4 gene polymorphism on vascular complications in type 2 diabetes patients.
OBJECTIVE
The aim of our study was to assess the association between the TLR4 Asp299Gly polymorphism and vascular complications in patients with type 2 diabetes.


METHODS
We examined 1090 patients with T2DM and 716 healthy controls. All subjects were genotyped for the Asp299Gly polymorphism by polymerase chain reaction (PCR) and restriction analysis.


RESULTS
The genotype frequencies of the Asp299Gly polymorphism were similar in T2DM patients and controls (p=0.512 and 0.311, respectively). The polymorphism was analyzed in subgroups of patients with macro- and microvascular complications. The distribution of genotypes was significantly different between patients with CVD and those without CVD. A significant increase of G allele frequency was observed in CVD+ patients, with odds ratio 2.06 (1.27-3.34), p=0.0035. The same effect was found when patients with diabetic retinopathy were compared with those without it (OR for G allele 2.12, 95% CI 1.43-3.12, p=0.0002). There were no statistically significant differences in genotype distribution between patients with diabetic nephropathy or neuropathy and those without these complications.


CONCLUSIONS
The results of our study demonstrated that the G allele of the Asp299Gly polymorphism of the TLR4 gene is associated with increased risk of cardiovascular disease and diabetic retinopathy in type 2 diabetes patients.
Department of Nephrology, Medical University of Lublin, Lublin, Poland. Electronic address: monika.buraczynska@umlub.pl.
Monika
M
Buraczynska
Department of Nephrology, Medical University of Lublin, Lublin, Poland.
Pawel
P
Zukowski
Department of Nephrology, Medical University of Lublin, Lublin, Poland.
Katarzyna
K
Ksiazek
Department of Cardiology, Medical University of Lublin, Lublin, Poland.
Piotr
P
Wacinski
Department of Nephrology, Medical University of Lublin, Lublin, Poland.
Michal
M
Dragan
D000328:Adult; D000368:Aged; D000483:Alleles; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000235:genetics; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics; D003929:Diabetic Neuropathies / Q000209:etiology / Q000235:genetics; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
Cardiovascular disease; Gene polymorphism; Microvascular complications; Risk allele; TLR4; Type 2 diabetes