(CCTTT)(n) repeat polymorphism in the NOS2 gene promoter is associated with atopy

Background: Several studies have shown that nitric oxide (NO) plays a role in the regulation of the T(H)1/T(H)2 balance, indicating the potential for NO to contribute to the development of atopy and several other allergic dis eases, including bronchial asthma. NO synthase 2 (NOS2) is critically invol ved in the synthesis of NO during several inflammatory states, and the gene encoding NOS2 is located at chromosome 17q11.2-q12, where 2 genome scans h ave identified a candidate locus for atopy and asthma. Objective: The 14-repeat allele of the (CCTTT)(n) repeat polymorphism in th e NOS2 promoter region is a powerful enhancer of promoter activity in repor ter constructs in vitro. We tested whether this potentially functional alle le in the NOS2 gene influences the development of atopy and asthma. Methods: We studied a total of 497 unrelated Japanese subjects (141 nonatop ic healthy controls, 102 atopic healthy controls, 56 nonatopic asthmatic su bjects, and 198 atopic asthmatic subjects). The odds ratio (OR) was calcula ted for atopy and asthma in carriers of the 14-repeat allele through use of logistic regression models. Atopy was defined as a positive specific IgE l evel to at least 1 of 10 common inhaled allergens. Results: The 14-repeat allele was inversely associated with atopy (OR = 0.4 2, P < .01). The association remained significant when the model was contro lled for asthmatic status (OR = 0.36, P < .01). This allele, however, was a ssociated neither with the development of asthma nor with total serum IgE l evels. Conclusion: Our findings suggest that the (CCTTT)(n) repeat polymorphism in the promoter of the NOS2 gene that affects promoter activity is a risk fac tor for the development of atopy, and this genetic effect seems independent of asthma.