Table 4. Pharmacogenetic studies.
| Definition of exacerbation | Gene | Associated variants | Reference Number |
|---|---|---|---|
| ER visit, hospitalization, or OSB | ADRB2 | rs1042713 | 47 |
| # Data from 4,226 children of white Northern European and Latino origin were analyzed, and the OR for AE increased by 1.52 (95% CI=1.17-1.99, P=0.0021) for each copy of the mutant allele of rs1042713 among the children treated with ICSs plus LABAs but not for treatment with ICSs alone or ICSs plus LTRAs or ICSs plus LABAs plus LTRAs. | |||
| ER visit, hospitalization, or OSB | ADRB2 | rs1042713 | 48 |
| # This pharmacogenetic analyses of two randomized studies to assess ICA plus LABA on AE showed that genotypes of rs1042713 had no effect on the percentage of adult asthmatics with severe AEs across all treatment groups | |||
| ER visit, or hospitalization | FCER2 | rs28364072 | 50 |
| # This study demonstrated associations between rs28364072 in FECR2 and severe AEs in 311 white and African American children enrolled in the CAMP trial (hazard ratio=3.95, 95% CI=1.64–9.51 and hazard ratio=3.08, 95%CI=1.00–9.47, respectively), despite ICS use. | |||
| ER visit, hospitalization, or OSB | FCER2 | rs28364072 | 51 |
| # This study analyzed data from 2 populations of childhood asthmatics in Europe using ICS. This report showed that rs28364072 in FECR2 was associated with increased risk of severe AEs (OR=1.91, 95%CI=1.08–3.40). | |||
| ER visit, hospitalization, or OSB | ST13 | rs138335 | 52 |
| # This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to AEs in children and young adults treated with ICS. It was a meta-analysis of three cohort studies in the UK and Netherlands. They found that rs138335 in ST13 was associated with an increased risk of hospitalization and OSB in the previous year (OR=1.22, P=0.013 and OR=1.22, P=0.0017, respectively). This association was replicated in the 3 independent cohorts in the US and the UK. | |||
| OSB | P2RX7 | rs2230911 | 53 |
| # A matched P2RX7 genetic case-control study was performed with samples from adult participants enrolled in the Asthma Clinical Research Network trial. African American carriers of the mutant allele of the rs2230911 (loss-of-function SNP) were more likely to have a history of OSB in the previous 12 months, with adjustment for ICS and LABA (OR = 2.7, 95%CI = 1.2-6.2, P=0.018). | |||
| ER visit, hospitalization, or OSB | CMTR1 | rs2395672 | 54 |
| # This is a GWAS of 237,726 common, independent markers was conducted in 806 Caucasian asthmatic patients from 2 population-based biobanks in US (both children and adult were included). Rs2395672 in CMTR1, was associated with an increased risk of AEs in both populations (OR=1.07, 95%CI=1.03-1.11, joint P=2.3×10−06). | |||
| ER visit, hospitalization, or OSB | LTC4S, LTA4H | rs730012, rs2660845 | 55 |
| # This is a prospective pharmacogenetic study to compare the efficacy of theophylline and montelukast as an add-on therapy in adult asthmatics in the US. Heterozygotes of rs730012 in LTC4S receiving montelukast had a 76% reduced risk of having an AE compared with reference allele homozygotes (P=0.023). For rs2660845 in LTA4H, the risk of having at least 1 AE was 4- to 4.5-fold higher in heterozygotes and mutant allele homozygotes compared with reference allele homozygotes. | |||
| ER visit, hospitalization, or OSB | IL4RA | rs8832 | 58 |
| # This is a pharmacogenetic analysis performed in a phase 2b clinical trial of pitrakinra, an IL-4Ra antagonist. A total of 407 non-Hispanic white adult asthmatics were enrolled, and 21 tagging and nonsynonymous SNPs in IL4RA were genotyped. Subjects homozygous for the rs8832 common alleles randomized to pitrakinra (placebo group nonsignificant) had decreased AEs. There was also a significant pitrakinra dose-response relationship for AEs in subjects homozygous for the common allele in rs8832 (P=0 .009). | |||
AE, Asthma exacerbation; CAMP, Childhood asthma management program; CI, Confidence interval; ER, Emergency room; ICS, Inhaled corticosteroid; LABA, Long acting β2-agonist; LTRA, Leukotriene receptor antagonist; OR, Odds ratio; OSB, Oral steroid burst; SNP, Single nucleotide polymorphism.