title: Polymorphism in Osteopontin Gene (SPP1) Is Associated with Asthma and Related Phenotypes in a Puerto Rican Population.
abstract: Recent studies have shown that osteopontin, a cytokine with suggested immunoregulatory functions, may contribute to pathogenesis of asthma. To determine whether single-nucleotide polymorphisms (SNPs) in SPP1, the gene encoding osteopontin, are associated with risk of asthma, we genotyped 6 known SNPs in SPP1 in the well-characterized Genetics of Asthma in Latino Americans population of 294 Mexican and 365 Puerto Rican parent-child asthma trios. The associations between SNPs and asthma or asthma-related phenotypes were examined by transmission disequilibrium tests as implemented in the family-based association test program. Three polymorphisms, 1 in exon 7 (rs1126616C) and 2 in the 3'-untranslated region (rs1126772A and rs9138A) of SPP1, were associated with diagnosis of asthma, severity of asthma, asthma in subjects with elevated immunoglobulin E (IgE) (IgE >100 IU/mL), and postbronchodilator FEV(1) in Puerto Ricans (P values=0.00007-0.04). The CC genotype of rs1126616 conferred an odds ratio of 1.7 (95% CI=[1.3, 2.3], P value adjusted for multiple comparisons=0.001) for asthma compared with the CT and TT genotypes. Furthermore, haplotype analysis identified rs1126616C-rs1126772A-rs9138A to be associated with an increased risk for asthma, severity of asthma, and asthma in subjects with elevated IgE (P=0.03). There was no association between the SPP1 SNPs and asthma outcomes in Mexicans. Our findings suggest that the SPP1 gene is a risk factor for asthma and asthma-related phenotypes in Puerto Ricans, and are consistent with previous animal and human studies on the role of osteopontin in pathogenesis of asthma.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Arjomandi
authors.forename: Josh M
authors.initials: JM
authors.lastname: Galanter
authors.forename: Shweta
authors.initials: S
authors.lastname: Choudhry
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.forename: Kenneth
authors.initials: K
authors.lastname: Beckman
authors.forename: Rocío
authors.initials: R
authors.lastname: Chapela
authors.forename: José R
authors.initials: JR
authors.lastname: Rodríguez-Santana
authors.forename: William
authors.initials: W
authors.lastname: Rodríguez-Cintrón
authors.forename: Jean
authors.initials: J
authors.lastname: Ford
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard