Relationship between COPD and polymorphisms of HOX-1 and mEPH in a Chinese population

Abstract

Abstract. Recent studies have proposed that susceptibility to chronic obstructive pulmonary disease (COPD) might be related with the polymorphisms of some genes encoding antioxidant enzymes, such as heme oxygenase-1 (HOX-1) and microsomal epoxide hydrolase (mEPH). We examined these polymorphisms in 256 patients with COPD and 266 healthy smokers from Han population in Southwest China. The frequencies of each allele were compared both individually and in combination between patients and controls. Polymorphisms of HOX-1 gene could be grouped into three classes: S (≤25 repeat), M (26-31 repeat), and L (≥32 repeat). The allele frequencies of class L and the genotypic frequencies of the group with L were significantly higher in COPD than in controls. Our findings also showed that the proportion of slow mEPH activity was significantly higher in COPD than in controls. Conversely, the proportion of fast mEPH activity was significantly lower in COPD. In combined analysis, the frequency of the individuals having at least one L allele in the HOX-1 gene promoter and slow or very slow activity genotype for mEPH was higher in COPD than in control. Genetic polymorphisms in HOX-1 and mEPH genes are associated with the development of COPD in Southwest China.

Heme oxygenase-1, a critical arbitrator of cell death pathways in lung injury and disease

“…Multiple human genetic epidemiology studies have examined the association between this length polymorphism in the human ho-1 gene, and COPD-related traits. The “Long” allele of the GT repeat (≥25, ≥30, ≥32, or ≥33 repeats, depending on study) has been associated with COPD [109], emphysema [108], COPD severity [110], lung function decline in COPD [111] and lung function decline in the general population [112–114]. For example, in a retrospective study of French smokers the L allele [(GT)n ≥ 33] was associated with decreased lung function parameters relative to non-carriers.…”

EPHX1polymorphisms, COPD and asthma in 47,000 individuals and in meta-analysis

“…They do not find any effect on the risk of COPD for either the T113C or the A139G polymorphisms. [13] HERSH [28] FU [27] BRØGGER [2] CHENG [26] PARK [25] ZIDZIK [24] VIBHUTI [23] MATHESON [22] KORYTINA [20] BUDHI [19] RODRIGUEZ [18] XIAO [17] TAKEYABU [16] YIM [15] PARK [14] SMITH [21] CHAPPELL [7] Overall . Meta-analysis of EPHX1 A139G genotype and risk of chronic obstructive pulmonary disease (COPD); overall and stratified analyses using both random and fixed effect models.…”

“…[2,7,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]) investigating the EPHX1 T113C and A139G polymorphisms in relation to COPD or emphysema as the primary end-point were included. Two minor studies were excluded from the analyses, because we were unable to retrieve the original papers despite contacting the corresponding authors.…”

What can naturally occurring mutations tell us about the pathogenesis of COPD?

“…Yamada and colleagues found a higher proportion of long repeats in patients with COPD and also showed that long repeats were associated with impaired promoter activity 52. Attempts to reproduce this effect have had varied success 38 50 53 54. In one study an attempt was made to replicate the association in both a case-control study and family-based study 39.…”