Investigation of the effect of nucleotide binding and oligomerization domain 2 (Nod2) gene variants on development and severity of chronic obstructive pulmonary disease (COPD)

Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent air flow limitation caused by enhanced chronic inflammatory response to the noxious particles and gases in the lung and the air ways. Even exposure to cigarette smoke is the most important risk factor for COPD, development of COPD only in 10-20% of habitual smokers exhibits the importance of genetic factors which could be effective on this disease. In recent years, it has been proposed that innate immune system receptors play role on patophsiology of COPD. NOD2 is one of these innate immune system receptors and play role in inflammatory processes. Aim of the present study was to investigate the effect of NOD2 gene rs2066844, rs1077861 and rs3135500 polymorphisms on development and severity of COPD by comparing genotype and allel frequency of these polymorphisms among both COPD patients and control group and patient subgroups categorized according to various parameters. Thus genotyping of 168 COPD patients and 100 controls was performed by using PCR-RFLP and Real Time PCR methods. Our results revealed that there were not any significant differences in terms of genotype and allel frequencies of rs2066844, rs1077861 and rs3135500 polymorphisms between patient and control groups. We did not found any association between these polymorphisms and COPD risk. In addition it was observed that family history, older age and higher amount of cigarette smoke (pack-year) increased the risk of COPD development. On the other hand, annual FEV1 decrease was higher in the patients carrying rs3135500 polymorphism GG genotype. No differences in genotype and allel frequencies of polymorphisms were detected between patients with and without frequent exacerbations and among moderate, severe and very severe patients (p0,05). Moreover, no differences were found in terms of genotype and allele frequencies among A, B, C and D patients and between patients with and without family history of COPD (p0,05). Minor allel frequency of rs2066844 polymorphism was lower than other studies conducted on Turkish population and rs1077861 polymorphism's minor allel frequency was found higher than other studies in the literature. Consequently, our results indicate that NOD2 gene rs2066844, rs1077861 and rs3135500 polymorphisms are not associated with development of COPD, but rs3135500 polymorphism GG genotype can be associated with progression of the disease.