COPD Pharmacogenetics Studies: Other Genes
Some other candidate genes have been analyzed in COPD pharmacogenetic studies in addition to the ADRB2 gene. An insertion–deletion polymorphism in the HCK gene that was associated with Hck protein levels has been identified in healthy individuals. In a lung health study (n = 487), the polymorphism was not associated with a decline in lung function, but with acute BDR. Several SNPs in five other candidate genes including EPHX1, SFTPB, TGFB1, SERPINE2 and GSTP1 have also been examined because these genes had been previously associated with COPD or related traits. Three SNPs in EPHX1 and three SNPs in SERPINE2 were associated with various BDR phenotypes in the NETT study (n = 389). In families from the Boston Early-Onset COPD Study, the rs1009668A SNP located on the EPHX1 gene showed replicated association with BDR.
In patients with asthma, SNPs at the gene encoding CRHR1 are an important determinant of response to ICS treatment. Another study investigated the association between the change in lung function in response to ICSs and CRHR1 SNPs in COPD patients. A total of 87 COPD patients were genotyped for three SNPs previously associated with ICS response in asthma. One intronic variant (rs242941) was associated with a change in FEV1 after a 12-week course of treatment with ICSs combined with a LABA.
Tantisira et al. reported a significant association between the GLCCI1 polymorphism (rs37972) and the response to glucocorticoid therapy in asthmatic patients. On the basis of this finding, the genetic impact of the polymorphism on glucocorticoid response in patients with COPD was also investigated. Genotyping 63 study participants in the 30-month Groningen and Leiden Universities Study of Corticosteroids in Obstructive Lung Disease found a significant association of the GLCCI1 genotype with improvement in FEV1 in COPD patients. The same allele was associated with better responses in both studies, indicating that GLCCI1 is associated with glucocorticoid response not only in asthma but also in COPD.
The CYP1A2 enzyme is thought to be involved in the metabolism of theophylline, and a pharmacogenetic study of theophylline showed the importance of alterations in CYP1A2.