The Efficacy Of Fluticasone Proprionate Versus Montelukast In Different Genotypes Of ASP299GLY TLR-4 Polymosphisms In Adult Asthmatics
Monday, March 5, 2018
South Hall A2 (Convention Center)
Yuriy Bisyuk, Andriy Kurchenko, Andriy Dubovyi, Lawrence Dubuske
RATIONALE: The Asp299Gly polymorphism (rs4986790) of the TLR4 gene leads to a single nucleotide substitution of adenine (A) for guanine (G) at position of +896 exon 4. The AG genotype is associated with atopic asthma and AA genotype with non-atopic asthma.

METHODS: 39 adults with mild persistent asthma were studied, 21 with AA and 18 with AG genotypes. The study had 2 periods: a 2-week run-in period, when all patients received low dose (125 μg) fluticasone propionate (FP) once a day; a 24-week treatment period, when patients took either FP once daily or montelukast 10 mg daily. 11 patients with AA (AA-FP) and 9 with AG (AG-FP) took FP. 10 patients with AA (AA-M) and 9 with AG (AG-M) took montelukast. Single nucleotide polymorphism of A896G (rs4986790) was detected by PCR.

RESULTS:: FP used in AA genotype patients for 24 weeks was more effective than montelukast, based on significant increase in FEV1 (AA-FP – 93.99±5.52 vs AA-M – 87.25±5.57 %, p=0.012), improvement in asthma control (ACQ: AA-FP – 0.93±0.27 vs AA-M – 2.00±0.75 points, p=0.001) and quality of life (AQLQ(S): AA-FP – 5.88±0.31 vs AA-M – 5.41±0.43 points, p=0.012). The clinical efficacy of montelukast in AG genotype patients was superior to FP (FEV1: AG-FP – 86.24±5.82 vs AG-M – 92.41±5.48 %, p=0.035; ACQ: AG-FP – 1.49±0.51 vs AG-M – 1.03±0.34 points, p=0.043; AQLQ(S): AG-FP – 4.72±0.35 vs AG-M – 5.87±0.29 points, p=0.001).

CONCLUSIONS: The effectiveness of inhaled corticosteroids and leukotriene modifiers may relate to polymorphisms of Asp299Gly-TLR-4 in adult asthmatics.