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 diseases, including bronchial asthma. NO synthase 2 (NOS2) is critically involved 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 have identified a candidate locus for atopy and asthma. OBJECTIVE: The 14-repeat allele of the (CCTTT)(n) repeat polymorphism in the NOS2 promoter region is a powerful enhancer of promoter activity in reporter constructs in vitro. We tested whether this potentially functional allele in the NOS2 gene influences the development of atopy and asthma. METHODS: We studied a total of 497 unrelated Japanese subjects (141 nonatopic healthy controls, 102 atopic healthy controls, 56 nonatopic asthmatic subjects, and 198 atopic asthmatic subjects). The odds ratio (OR) was calculated 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 level to at least 1 of 10 common inhaled allergens. RESULTS: The 14-repeat allele was inversely associated with atopy (OR = 0.42, P < .01). The association remained significant when the model was controlled for asthmatic status (OR = 0.36, P < .01). This allele, however, was associated neither with the development of asthma nor with total serum IgE levels. CONCLUSION: Our findings suggest that the (CCTTT)(n) repeat polymorphism in the promoter of the NOS2 gene that affects promoter activity is a risk factor for the development of atopy, and this genetic effect seems independent of asthma.
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 diseases, including bronchial asthma. NO synthase 2 (NOS2) is critically involved 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 have identified a candidate locus for atopy and asthma. OBJECTIVE: The 14-repeat allele of the (CCTTT)(n) repeat polymorphism in the NOS2 promoter region is a powerful enhancer of promoter activity in reporter constructs in vitro. We tested whether this potentially functional allele in the NOS2 gene influences the development of atopy and asthma. METHODS: We studied a total of 497 unrelated Japanese subjects (141 nonatopic healthy controls, 102 atopic healthy controls, 56 nonatopic asthmatic subjects, and 198 atopic asthmatic subjects). The odds ratio (OR) was calculated 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 level to at least 1 of 10 common inhaled allergens. RESULTS: The 14-repeat allele was inversely associated with atopy (OR = 0.42, P < .01). The association remained significant when the model was controlled for asthmatic status (OR = 0.36, P < .01). This allele, however, was associated neither with the development of asthma nor with total serum IgE levels. CONCLUSION: Our findings suggest that the (CCTTT)(n) repeat polymorphism in the promoter of the NOS2 gene that affects promoter activity is a risk factor for the development of atopy, and this genetic effect seems independent of asthma.