NAD-DEPENDENT DEACETYLASE GENES OF SIRTUIN FAMILY AND RISK OF DEVELOPING VARIOUS PHENOTYPES OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases with high morbidity and mortality. The pathogenesis of COPD is closely related to oxidative stress, that is the main mechanism causes accelerated cell senescence. Published data suggest that the COPD pathogenesis may involve stress responses dysregulation that inhibit cellular senescence. We aimed to assess the contribution of sirtuin genes (SIRT2, SIRT1, SIRT3, SIRT6) to the various COPD phenotypes risk. SNPs of SIRT2 (rs10410544), SIRT1 (rs3758391, rs3818292), SIRT3 (rs3782116, rs536715), SIRT6 (rs107251) genes were genotyped by the real-time polymerase chain reaction (PCR) among 1245 samples (severe COPD with frequent exacerbations (N=331), stable COPD with rare exacerbations (N=290) and control (N=624)). Logistic regression was used to detect the association of studied SNPs in different models. Significant associations with severe COPD phenotype were identified for SIRT1 (rs3818292) (P=0.0097, OR = 1.49 for AG genotype), SIRT3 (rs3782116) (P = 0.0034, OR =0.63) and SIRT3 (rs536715) (P = 0.00001, OR =0.53) under dominant model, and SIRT6 (rs107251) (P = 0.00001, OR =0.55 for CT genotype). Stable COPD phenotype with rare exacerbations was associated with SIRT1 (rs3818292) (P = 0.0055, OR =1.54 for AG genotype), SIRT3 (rs536715) (P = 0.00001, OR =0.48 under dominant model), and SIRT6 (rs107251) (P = 0.0002, OR =0.54 for CT genotype). The obtained results indicate the contribution of NAD-dependent deacetylase genes of sirtuin family and cellular senescence mechanisms to COPD development. The SIRT3 (rs3782116) identified as a specific marker for severe COPD phenotype with frequent exacerbations.