The Role of SLC22A4 Gene Polymorphisms in the Response to Salbutamol in Asthmatic Patients

Abstract

Response to Bronchodilators is influenced by many factors including genetics. To evaluate the influence of SLC22A4 gene polymorphisms (rs3792876 and rs2073838) on the response to inhaled salbutamol in asthmatic patients, bronchodilator response was assessed in 180 bronchial asthma patients via measuring changes of the Forced Expiratory Volume in one second (FEV1) after the administration of inhaled salbutamol and genotyping for rs3792876 and rs2073838 was carried out using real-time polymerase chain reaction. Frequencies of genotypes were compared in between responders and non-responders. The frequency of rs2073838 genotypes showed no significant differences. On the other hand, the recessive genotype of rs3792876 occurred more frequently among the non-responding patients P = 0.01, 95% confidence interval (1.2-9.5). The homozygous form of rs3792876 can influence the absorption of inhaled bronchodilator (Salbutamol), although, replication studies on this point are recommended.

Lack of impact of OCTN1 gene polymorphisms on clinical outcomes of gabapentinoids in Pakistani patients with neuropathic pain

“…OCTN1 has been implicated in the uptake and altered metformin plasma concentration in OCTN1 L503F genetic variants [5,7]. A study has recently reported the impact of rs3792876 homozygous genotype in the improved clinical efficacy of inhaled salbutamol suggesting the role of OCTN1 in drug absorption [17]. Our results showed a lack of significant association of OCTN1 rs1050152 and rs3792876 genotypes on the clinical efficacy of gabapentinoids between nonresponders and responders (P = 0.718 and 0.314, respectively).…”

“…The main factors for nonadherence to the treatment were poor efficacy and tolerability of pregabalin [20]; however, the role of genetic variations of the transporters in relation to the therapeutic efficacy of the substrate drugs needs to be explored. The pharmacological and pathophysiological roles of common genetic variants of SLC22A4 OCTN1 rs1050152 and rs3792876 in the absorption and disposition of various drugs and autoimmune and inflammatory diseases have been reported in different studies [4][5][6][7][8][9]17]. The influence of the OCTN1 genetic variants on the uptake and clearance of substrate drugs might result in variable clinical outcomes.…”

“…The genetic variants of OCTN1 rs1050152 and intron 1 rs3792876 mutation affecting the binding of runt-related transcription factor 1 protein (RUNX-1) for transcription of SLC22A4 are reported to have a strong association with diabetes mellitus, inflammatory bowel disease, rheumatoid arthritis and autoimmune thyroiditis suggesting the involvement of SLC22A4 in the autoimmune regulatory pathway [13][14][15][16]. In addition, increased absorption of inhaled bronchodilator salbutamol with better clinical outcomes has been reported in asthmatic individuals with recessive genotype suggesting the role of rs3792876 homozygous variant in the absorption of OCTN1 drug substrates [17].…”