Relationship Between Chronic Obstructive Pulmonary Disease And Polymorphisms Of Heme Oxygenase-1 And Microsomal Epoxide Hydrolase In A Southwest Chinese Population

Oxidatibe stress is believed to play an important role in the pathogenesis of smoking-induced chronic obstructive pulmonary disease (COPD). Heme Oxygenase-1 (HOX-1) and Microsomal epoxide hydrolase (mEPH) play a protective role as an antioxidant enzyme in the lung. Genetic susceptibility to the development of COPD might depend on variation in the activities of HOX-1 and mEPH. It was investigated whether polymorphisms in HOX-1 and mEPH genes had any association with susceptibility to COPD.The genotypes of 63 patients with COPD and 61 control healthy subjects were determined by direct sequencing, polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP), and fragment analysis for mEPH enon3, exon4 genes, and HOX-1 respectively. All subjects were smokers in Han nationality of Southwest China. The frequencies of polymorphic genotypes of HOX-1 and mEPH enon3, exon4 genes were compared both individually and in combination between the patients with COPD and healthy smokers.According to the number of (GT)n repeat, polymorphisms of HOX-1 gene were grouped into three classes : S (≤25 repeat), M (26-31 repeat), L (≥32 repeat). The proportion of allele frequencies in class L, as well as the proportion of genotypic frequencies in the Groupl with class L alleles (L/S,L/M,L/L), was significantly higher in the smokers with COPD than in healthy smokers (L allele: 18.3% VS 6.5%, P<0.01; Genotype I: 28.6% VS 13.1%, P=0.035). Our findings also showed that the proportion of individuals with slow mEPH activity was significantly higher in patients with COPD than in control subjects (58.7% vs 32.8%, P<0.01). In contrast, the proportion of individuals with fast mEPH activity was significantly lower in patients with COPD than in control subjects (4.8% vs 19.7%, P<0.02). During combined analysis of the genetic polymorphisms for HOX-1 and mEPH, it was found that the frequency of the individuals having combination of the genotype representing at least one allele with large sizeof (GT)n repeat in the HOX-1 gene promoter region and slow activity genotype for mEPH was higher in COPD patients than control subjects (20.6% vs 6.6%, P=0.035).In conclusion, genetic polymorphisms in HOX-1 and mEPH genes are associated with the development of COPD in Southwest China. In addition, HOX-1 Groupl genotype (include L allele) and the heterozygous variant of mEPH exon3 are independent risk factors for developing COPD.