Lack of association between NOS2 pentanucleotide repeat polymorphism and asthma phenotypes or exhaled nitric oxide concentration

Nitric oxide (NO) plays an immunoregulatory role in balancing cellular immunity The expression of inducible nitric oxide synthase gene (NOS2) is upregulated upon exposure to proinflammatory cytokines and microbial exposure. The (CCTTT)n polymorphism in NOS2 promoter confers protection against infections and immunological disorders including atopy. We investigated the association between (CCTTT)n and asthma traits in Chinese children. Asthmatic children between 5 and 18 years of age and non-allergic controls were recruited. Plasma total and specific IgEs were measured by immunoassays, and exhaled NO concentration was quantified online by chemiluminescence. NOS2(CCTTT)n was genotyped by GeneScan analysis. The mean (SD) age of 291 asthmatics and 172 controls were 11.1 (3.8) years and 11.6 (4.0) years, respectively (P = 0.259). NOS2 (CCTTT)n followed Hardy-Weinberg equilibrium in both groups, and its uni-modal allele distribution peaks at 12-repeat. Significant interethnic differences in (CCTTT)n alleles were observed, with our Chinese having less 13-repeat (P-c = 0.022) but more 17-repeat (P-c=0.033) than Caucasians. The frequency of 14-repeat allele was similar in our Chinese as compared to Japanese (P-c = 0.32). Multivariate regression analyses failed to detect any association between this polymorphic marker and asthma diagnosis (P=0.949), atopy (P=0.305), IgE sensitization to aeroallergens (P>0.2 for all), or FeNO (P = 0.847). These findings do not support NOS2 to be a major candidate gene for asthma or IgE-mediated allergic diseases in Chinese children.