BACKGROUND: Polymorphisms in nitric oxide synthase genes (NOS1, NOS2, and NOS3) have been suggested to have a major impact on fraction of exhaled nitric oxide (FENO), a biomarker of airway inflammation. However, the genetic contribution of NOS polymorphisms to FENO is not fully understood. The aim of this study was to investigate comprehensively the association between single nucleotide polymorphisms (SNPs) in all three NOS genes and FENO in an adult population, and to assess whether such associations are modified by asthma or atopy. METHOD: In 1737 adults from a Swedish general population sample, FENO was measured and genetic variation in the NOS genes was assessed using 49 SNPs. The genetic effect of NOS polymorphisms on FENO, asthma, and atopy was estimated using multiple regression methods. RESULTS: In a multi-SNP model based on stepwise regression analysis, two SNPs in NOS2 and one in NOS3 showed independent associations with levels of FENO. For NOS2 SNP rs9901734, subjects had 5.3% (95% CI 1.0% to 9.7%) higher levels of FENO per G allele, and for rs3729508, subjects with CC or CT genotypes had 9.4% (95% CI 3.1% to 15.2%) higher levels compared with TT. For NOS3 SNP rs7830, subjects with GT or TT had 5.6% (95% CI 0.4% to 11.1%) higher levels than GG; the genetic effect of this SNP was stronger in asthmatics (21.9%, 95% CI 4.6% to 42.0%). CONCLUSION: These results suggest that NOS2 is the major NOS gene determining variability in exhaled nitric oxide in the healthy adult population, while NOS3 may play a more important role in asthmatic adults.
BACKGROUND: Polymorphisms in nitric oxide synthase genes (NOS1, NOS2, and NOS3) have been suggested to have a major impact on fraction of exhaled nitric oxide (FENO), a biomarker of airway inflammation. However, the genetic contribution of NOS polymorphisms to FENO is not fully understood. The aim of this study was to investigate comprehensively the association between single nucleotide polymorphisms (SNPs) in all three NOS genes and FENO in an adult population, and to assess whether such associations are modified by asthma or atopy. METHOD: In 1737 adults from a Swedish general population sample, FENO was measured and genetic variation in the NOS genes was assessed using 49 SNPs. The genetic effect of NOS polymorphisms on FENO, asthma, and atopy was estimated using multiple regression methods. RESULTS: In a multi-SNP model based on stepwise regression analysis, two SNPs in NOS2 and one in NOS3 showed independent associations with levels of FENO. For NOS2 SNP rs9901734, subjects had 5.3% (95% CI 1.0% to 9.7%) higher levels of FENO per G allele, and for rs3729508, subjects with CC or CT genotypes had 9.4% (95% CI 3.1% to 15.2%) higher levels compared with TT. For NOS3 SNP rs7830, subjects with GT or TT had 5.6% (95% CI 0.4% to 11.1%) higher levels than GG; the genetic effect of this SNP was stronger in asthmatics (21.9%, 95% CI 4.6% to 42.0%). CONCLUSION: These results suggest that NOS2 is the major NOS gene determining variability in exhaled nitric oxide in the healthy adult population, while NOS3 may play a more important role in asthmatic adults.
Authors: E Bouzigon; R Nadif; E E Thompson; M P Concas; S Kuldanek; G Du; M Brossard; N Lavielle; C Sarnowski; A Vaysse; P Dessen; R J P van der Valk; L Duijts; A J Henderson; V W V Jaddoe; J C de Jongste; S Casula; G Biino; M-H Dizier; I Pin; R Matran; M Lathrop; M Pirastu; F Demenais; C Ober Journal: Clin Exp Allergy Date: 2015-04 Impact factor: 5.018
Authors: Ralf Jp van der Valk; Liesbeth Duijts; Nicolas J Timpson; Muhammad T Salam; Marie Standl; John A Curtin; Jon Genuneit; Marjan Kerhof; Eskil Kreiner-Møller; Alejandro Cáceres; Anna Gref; Liming L Liang; H Rob Taal; Emmanuelle Bouzigon; Florence Demenais; Rachel Nadif; Carole Ober; Emma E Thompson; Karol Estrada; Albert Hofman; André G Uitterlinden; Cornélia van Duijn; Fernando Rivadeneira; Xia Li; Sandrah P Eckel; Kiros Berhane; W James Gauderman; Raquel Granell; David M Evans; Beate St Pourcain; Wendy McArdle; John P Kemp; George Davey Smith; Carla Mt Tiesler; Claudia Flexeder; Angela Simpson; Clare S Murray; Oliver Fuchs; Dirkje S Postma; Klaus Bønnelykke; Maties Torrent; Martin Andersson; Patrick Sleiman; Hakon Hakonarson; William O Cookson; Miriam F Moffatt; Lavinia Paternoster; Erik Melén; Jordi Sunyer; Hans Bisgaard; Gerard H Koppelman; Markus Ege; Adnan Custovic; Joachim Heinrich; Frank D Gilliland; Alexander J Henderson; Vincent Wv Jaddoe; Johan C de Jongste Journal: J Allergy Clin Immunol Date: 2013-12-06 Impact factor: 10.793
Authors: Yue Zhang; Muhammad T Salam; Kiros Berhane; Sandrah P Eckel; Edward B Rappaport; William S Linn; Rima Habre; Theresa M Bastain; Frank D Gilliland Journal: Environ Health Date: 2017-08-18 Impact factor: 5.984
Authors: Farzian Aminuddin; Tillie-Louise Hackett; Dorota Stefanowicz; Aabida Saferali; Peter D Paré; Amund Gulsvik; Per Bakke; Michael H Cho; Augusto Litonjua; David A Lomas; Wayne H Anderson; Terri H Beaty; Edwin K Silverman; Andrew J Sandford Journal: BMC Pulm Med Date: 2013-11-06 Impact factor: 3.317