Association of nitric oxide synthase gene polymorphism with asthma: A systematic review and meta‐analysis

INTRODUCTION: This study examines the associations between asthma and nitric oxide (NO) synthase (NOS) gene polymorphisms. METHODS: After a systematic literature search in electronic databases, studies were selected based on eligibility criteria. Data were extracted from research articles and were synthesized and tabulated. Where a particular polymorphism data were reported by multiple studies, meta‐analyses of odds ratios were performed, or odds ratios reported by individual studies were pooled. RESULTS: Twenty studies (4450 asthma patients and 5306 non‐asthmatic individuals) were identified. Many studies did not find any association between CCTTT repeat polymorphism in NOS2 gene and asthma. However, a study reported that pretreatment mean exhaled NO levels in asthmatics were found to be significantly higher in genotypes with higher number of CCTTT repeats. Also, alleles with <11 CCTTT repeats were associated with poor asthma treatment outcomes. A single nucleotide polymorphism, G894T, in NOS3 gene was not found to be significantly associated with asthma by at least four studies. However, a T allele at this locus was associated with lower NO levels. Also, G894T frequency was significantly higher in asthmatic children who responded to inhaled corticosteroids along with long‐lasting beta2‐agonists. A T allele of NOS3 786C/T polymorphism increased the probability of bronchial asthma with comorbid essential hypertension in asthma patients. Asthma severity also differed for different Ser608Leu exon 16 variants of NOS2 gene. CONCLUSIONS: Several polymorph NOS gene variants are identified, some of which appear to have influence on asthma prevalence or outcomes. However, data are varying depending on the nature of variant, ethnicity, study design, and disease parameters.