Association between pentanucleotide repeat polymorphism in NOS2 promoter and asthma exacerbations
| Autor: | Keita Hirai, Kazuyuki Inoue, Masayuki Suzuki, Toshihiro Shirai, Kunihiko Itoh, Daiki Tsuji |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
biology business.industry Odds ratio respiratory system Stepwise regression medicine.disease Gastroenterology Peripheral blood mononuclear cell Nitric oxide synthase medicine.anatomical_structure Internal medicine White blood cell Exhaled nitric oxide medicine biology.protein Allele business Asthma |
| Zdroj: | Molecular Pathology and Functional Genomics. |
| Popis: | Introduction: Polymorphisms of inducible nitric oxide synthase (NOS2) gene is related to fractional exhaled nitric oxide (FeNO) level in steroid-naive patients with asthma, but its association with treatment outcomes remains unclear. Aims and objectives: We investigated the association of NOS2 polymorphism with exacerbations in patients with asthma. Methods:NOS2 pentanucleotide repeat (CCTTT)n polymorphisms were genotyped in 136 patients with moderate/severe asthma. Cross-sectionally, we evaluated NOS2 mRNA expression levels in peripheral blood mononuclear cells, FeNO levels, white blood cell counts and lung function. Exacerbations were recorded one year before and after the cross-sectional study. Results: The repeat number ranged from 9 to 22, with 13 being the most frequent allele. Relative NOS2 mRNA expression levels were significantly different among patients with the shorter allele having ≤11 repeats (n = 59), those with 12 (n = 39) and those with ≥13 (n = 38), with medians of 18.7 [95% confidential interval (CI) 14.7–21.0], 11.5 (9.9–21.1) and 9.6 (7.2–13.3), respectively. FeNO levels were not significantly associated with repeat numbers. Exacerbations were observed in 43 patients over a period of two years. Stepwise logistic regression analysis revealed that having shorter alleles with ≤11 repeats [odds ratio (OR), 2.7; 95% CI, 1.2–6.2], forced expiratory volume in 1 s (FEV1) Conclusions:NOS2 pentanucleotide repeat polymorphisms contributed to varying mRNA expression levels and affected asthma exacerbations. |
| Databáze: | OpenAIRE |
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