Association between (CCTTT)n repeat polymorphism in NOS2 promoter and asthma exacerbations

TH2 cytokines induce the expression of inducible nitric oxide synthase (NOS2) in bronchial epithelial cells. [...]the fractional exhaled nitric oxide (Feno) level is a useful surrogate biomarker for eosinophilic airway inflammation. [...]the present study demonstrates the association between pentanucleotide repeat polymorphism in the NOS2 promoter region and changing gene expression levels. [...]it is suggested that having alleles shorter than or equal to 11 repeats contributes to the worsening of clinical outcomes following asthma treatment in patients with moderate to severe asthma.Methods Study subjects Subjects included 136 patients with moderate to severe asthma from the previous study performed in Shizuoka General Hospital between February and December 2015.E1 All patients with asthma fulfilled the definition given by GINA and were categorized as having moderate (GINA step 3) or severe (GINA step 4-5) asthma.E2 Study subjects underwent evaluation to determine NOS2 mRNA expression levels in PBMCs, Feno levels, white blood cell counts, and lung function in a cross-sectional study. Characteristic All subjects (n = 136) S/S + S/L (n = 59) L/L (n = 77) P value Age (y) 66 (50-74) 64 (45-73) 67 (54-75) .254 BMI (kg/m2) 23.1 (20.7-25.4) 23.9 (20.7-26.0) 22.8 (20.7-25.2) .213 Sex: male 63 (46) 26 (44) 37 (48) .644 Childhood onset 25 (18) 14 (24) 11 (14) .184 GINA treatment step Step 5 13 (10) 8 (14) 5 (6) .375 Step 4 76 (56) 32 (54) 44 (57) Step 3 47 (35) 19 (32) 28 (36) Atopy 101 (74) 47 (80) 54 (70) .208 Allergic rhinitis 81 (60) 36 (61) 45 (58) .762 Smoking status Current smoker 4 (3) 2 (3) 2 (3) .900 Ex-smoker 58 (43) 24 (41) 34 (44) Never smoker 74 (54) 33 (56) 41 (53) Pack-years 0 (0-16) 0 (0-17) 0 (0-15) .752 FEV1% predicted 83.4 (68.1-95.4) 86.1 (71.8-95.6) 81.9 (67.1-94.9) .283 FEV1/FVC 69.5 (62.5-76.1) 71.7 (65.7-78.6) 67.7 (60.8-74.8) .038 Feno (ppb) 30.0 (16.9-48.2) 29.3 (15.1-55.6) 30.8 (19.5-47.7) .683 Total IgE (IU/mL) 239 (88-644) 274 (91-986) 233 (84-558) .351 NOS2 mRNA level 14.5 (8.2-22.2) 18.7 (12.1-26.4) 11.2 (6.6-20.1) .001 Plasma NOx (ng/mL) 38.6 (28.6-60.7) 36.6 (27.4-61.9) 42.5 (30.7-55.9) .445 Peripheral blood cells (cells/μL) Neutrophil 3602 (2975-4636) 3548 (3065-4995) 3743 (2930-4516) .928 Lymphocyte 1683 (1371-2100) 1684 (1362-2087) 1670 (1373-2101) .696 Monocyte 367 (300-461) 364 (293-467) 368 (306-461) .836 Eosinophil 337 (206-521) 316 (213-553) 351 (202-509) .802 Basophil 43 (31-63) 41 (31-71) 49 (33-61) .816 ICS dose (μg/d) 3