Genetic biomarkers for risk prediction of chronic obstructive pulmonary disease (COPD) in smokers and non-smokers

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease and not fully reversible. It is the 3rd major cause of death worldwide and ranks 2nd in India. Although the primary etiopathogenic factor is chronic exposure to tobacco smoke, it has been observed that all smokers do not develop COPD and many non-smokers suffer from the disease. This difference in susceptibility can be attributed to individual genetic variations. Therefore, the present study was conducted to analyze the association of genetic variants in candidate genes with COPD susceptibility among smokers and non-smokers. A total of 500 subjects were enrolled in the study (250 each of controls and cases) after ethical approval and informed consent. Fifteen single nucleotide polymorphisms (SNPs) in eight genes viz.IL-1RN, IL-1B, IL-6, TNF-A, SOD2, CAT, ADAM33 and AQP5 were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Data was analyzed using SPSS (ver 21.0) and association with smoking status was determined. Among 250 healthy controls enrolled, 119 were non-smokers and 131 were smokers. Out of 250 COPD cases, only 34 were non-smokers and rest 216 were smokers. The genotypic frequencies of IL-1RN intron2 86 bp VNTR (I,II), IL-1 & beta; -511 T/C, IL-6 -597A/G, TNF-& alpha; -308G/A, SOD2 + 47C/T, CAT - 21A/T and AQP5 promoter G/A were significantly associated with smoking. Among 07 ADAM33 SNPs, the genotype frequencies of V4exon22C/G and F + 1intron6C/T were significantly associated in smokers, while V1exon22G/T, S2exon19G/C, S1exon19A/G and Q1intron16A/G were associated with non-smokers. The genetic variants (SNPs) in smokers and non-smokers showing differential association with the risk of COPD can be identified as predictive biomarkers.