title: Physician-diagnosed asthma and acute chest syndrome: associations with NOS polymorphisms.
abstract: The main objectives of this paper were to test the hypothesis that polymorphisms in NOS1 and NOS3 genes associate with ACS in SCD patients and to characterize the association between physician-diagnosed asthma and acute chest syndrome (ACS). Case-control study of sickle cell disease patients >or=5 years old with ACS (cases; n=86) and those without ACS (controls; n=48) was carried out. Associations between ACS and the AAT repeat in intron 13 (formerly intron 20) of the NOS1, and with NOS3 T-786C polymorphism were explored. Physician-diagnosed asthma was determined by chart review, patient- or parent (guardian)-reported asthma, and drug use. Eighty five percent of participants with asthma had at least one episode of ACS compared to 14.6% of controls: adjusted odds ratio (OR) (95%CI) 5.46 (2.20,13.5), P= or<0.0001. Asthma correlated with the number of episodes of ACS (P<0.001). NOS1 AAT repeat polymorphism associated with the risk of ACS (P=0.001) in patients without physician-diagnosed asthma. No associations were found between the genotype of the NOS3 T-786C SNP and ACS. Physician-diagnosed asthma is a major risk factor for ACS. NOS1 AAT repeat polymorphism may contribute to physician-diagnosed asthma.
authors.affiliation: Pharmacogenetics Center, Nemours Children's Clinic, Jacksonville, Florida 32207, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Duckworth
authors.forename: Lewis
authors.initials: L
authors.lastname: Hsu
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.forename: James E
authors.initials: JE
authors.lastname: Sylvester
authors.forename: Niranjan
authors.initials: N
authors.lastname: Kissoon
authors.forename: Eric
authors.initials: E
authors.lastname: Sandler
authors.forename: John J
authors.initials: JJ
authors.lastname: Lima
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications*; D001249:Asthma / Q000175:diagnosis; D044383:Black People; D016022:Case-Control Studies; D002637:Chest Pain / Q000209:etiology*; D002648:Child; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007438:Introns; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D013577:Syndrome
chemical_list: D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III