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Polymorphisms of TLR2 (Arg753Gln) and TLR4 (Asp299Gly) genes and COPD: The Croatian study

Chronic obstructive pulmonary disease (COPD) is a disease defined by progressive development of irreversible airflow limitation typically determined by reduction of quantitative spirometric parameters like forced expiratory volume at 1s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC, FEV1/FVC). The current understanding of pathogenesis includes complex interaction between environmental factors and genetic predisposition. The major environmental risk factor is cigarette smoke, while candidate genes that may influence a person's risk for COPD development are still under study. Toll like receptors are members of transmembrane proteins that recognize conserved molecular motifs of viral and bacterial origin and initiate innate immune response. In COPD patients, recurrent infections of the lower bronchial tree with different bacteria and viruses, are present, suggesting a defect in immune response initiation. Therefore, the aim of this study was to investigate the potential association of polymorphisms in TLR2 (Arg753Gln) and TLR4 (Asp299Gly) genes and risk of COPD. The study group comprised of patients with COPD (n=106) and healthy controls (n=48). COPD was diagnosed by pulmonology specialist according to clinical examination and spirometry results FEV1/FVC < 0.70 and FEV1 <80% predicted. DNA was isolated from whole blood and subjected to genotyping with TaqMan SNP Genotyping Assays of interest, using AB 7500 Real Time PCR System (Applied Biosystems). In this study, only two genotypes for each of the polymorphism were determined, homozygote with major allele (GG for TLR2 ; AA for TLR4) and heterozygote. Homozygous carriers of the minor alleles were not detected. No significant deviations from the Hardy Weinberg equilibrium for either TLR2 (Arg753Gln) or TLR4 (Asp299Gly) polymorphisms were observed. There were no statistical significant differences in allele (TLR2: X2=0.003 ; P=0.955 ; OR=1.83 ; 95%CI=0.20-16.57 ; TLR4: X2=0.011 ; P=0.914 ; OR=0.82 ; 95%CI=0.29-2.89) or genotype frequency distribution (TLR2: X2=0.003 ; P=0.954 ; TLR4: X2=0.013 ; P=0.911 ; ) of the tested polymorphisms between COPD patients and healthy controls. According to obtained results, it seems that polymorphisms in TLR2 (Arg753Gln) and TLR4 (Asp299Gly) genes are not associated with development of COPD in the population of Croatia. Our results suggest that further studies based on a larger number of samples are needed to confirm or reject the reported conclusion.

TLR2; TLR4; chronic obstructive pulmonary disease; polymorphisms

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