engleski

Gene expression and genetic variations of HSP70, TLR2 and TLR4 in COPD

Complete molecular mechanisms that underlie inflammatory responses in chronic obstructive pulmonary disease (COPD) are still unknown but seem to be associated with chronic exposure to noxious particles or gases, particularly cigarette smoke, and genetic susceptibility. The aim of this study was to explore gene expressions of HSP70 as well as TLR2 and TLR4 (the main receptors for extracellular Hsp70), and association of their polymorphisms with risk of COPD. 137 patients with stable COPD and 95 controls were included in the study. Real-time polymerase chain reaction was used for the determination of HSP70, TLR2 and TLR4 mRNA expressions as well as for genotyping for single nucleotide polymorphisms (SNPs) of HSP70 (rs1008438, rs6457452), TLR2 (rs1898830, rs3804099, rs13150331) and TLR4 (rs2737190, rs10759932, rs7846989) genes. Levels of HSP70 (P<0.001) and TLR2 (P=0.002) mRNA expression were increased in COPD patients compared to healthy subjects and were also increased at each disease stage regarding the airway obstruction (GOLD 2-4 with P<0.001, P=0.019, respectively) as well as in each group based on symptoms severity assessed by CAT and history of exacerbations (GOLD A-D with P<0.001, P=0.009, respectively) compared to controls. TLR4 gene expression was similar in controls and COPD patients. After smoking adjustments, A/C genotype of SNP rs1008438 of HSP70 gene showed to be associated with a decreased risk of COPD in Croatian population in overdominant model with OR (95% CI) of 0.52 (0.28- 0.96) (P=0.036). Enhanced gene expression of HSP70 and TLR2 might be involved in immune response in stable COPD, while HSP70 rs1008438 variation might play important role in the genetic susceptibility to COPD.

chronic obstructive pulmonary disease ; heat shock protein 70 ; single nucleotide polymorphism ; toll-like receptor 2 ; toll-like receptor 4

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