NOS1 polymorphism is associated with atopy but not exhaled nitric oxide levels in healthy children

Abstract

Exhaled nitric oxide (FENO) is raised in atopy. The mechanism for this is unclear. The aim of this study was to investigate whether the number of AAT repeats in intron 20 of the NOS1 gene, recently associated with variations in FENO in adults with asthma and cystic fibrosis, was associated with the raised FENO in healthy atopic children. Eighty-seven healthy children (44 girls, 42 atopic, age range 6-18 years) underwent measurements of FENO, spirometry, airway responsiveness and skin prick testing. Genotyping was carried out to determine the number of AAT repeats. There was no association between the number of AAT repeats and FENO in either the whole sample of healthy children (n = 87) or in the subsample of healthy atopics (n = 42). However, a greater number of atopic children had two high repeat alleles compared with non-atopic children (33.3% vs. 13.6%, respectively, p = 0.03). This suggests that variations in the NOS1 gene may contribute to atopy without this relationship being reflected by FENO.

A NOS1 Gene Polymorphism Associated with Asthma and Specific Immunoglobulin E Response to Mite Allergens in a Colombian Population

“…Furthermore, in Chinese subjects this polymorphism was also associated with specific IgE to D. pteronyssinus, as detected by skin test [13]. Our results support these and other data [31] suggesting that NOS1 , or a close linked gene, could be influencing the IgE response. However, contrarily to the expected, we found no association of IgE levels with the C5266T SNP but with the CA repeat of exon 29, being the third polymorphism of NOS1 gene associated with this phenotype.…”

“…Several authors have speculated about the physiological basis for associations between NOS1 gene and asthma or atopy [27, 31]. Our finding that allele 16 is associated with asthma and also with low total and specific IgE levels is unexpected and intriguing.…”

“…NOS1 polymorphisms have been associated with asthma [9, 27, 28], IgE levels [13,29,30,31] and exhaled NO concentration [32]. The three studies showing association with asthma were performed in Caucasian and Japanese populations, two of them with the NOS1 intron 2 CA repeat and the other with the exon 29 CA repeat.…”

Effects of age, gender, and environmental exposures on exhaled nitric oxide level in healthy 12 to 18 years Qatari children

“…[2728] In children, there is a recent evidence of an association between NOS polymorphism and atopy as well as asthma and FENO level. [252930] Another explanation for the ethnic difference in FENO levels may be related to the difference in the alveolar surface area that affect the amount of NO produced and hence exhaled. This may be explained by correlation of FENO with the weight, surface area,[14] height,[1419] and pulmonary function test parameters[42531] in different studies among children.…”

Single nucleotide polymorphisms in theNOS2andNOS3genes are associated with exhaled nitric oxide

“…A reported association between AAT repeats in intron 20 in NOS1 and higher FENO levels in asthmatic adults16 was not replicated in asthmatic children 17 18 20. A recent population based study found tag single nucleotide polymorphisms (SNPs) in NOS2 to be significantly associated FENO and the association was stronger in asthmatic children 21.…”