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.

Involvement of lymphocytes in asthma and allergic diseases

“…Higher co-expressing T-bet(þ) GATA-3(þ) cells in the eosinophil-high asthmatics after in-vitro stimulation implies the involvement of T cell plasticity in the pathogenesis of asthma [36 regulated (summarized in the list below) by: the methylation status of Treg-specific demethylated region in the enhancer through complex signals from T cell receptors, tranforming growth fcatorb, IL-2 and IL-6 cytokines and other active mechanisms in the thymus [37,38 & ]; histone tail modification by various chromatin modifying/ remodeling proteins, for example, histone/protein deacetylases inhibit Foxp3 gene expression and Treg function, [38 & ,39]; and microRNA, for example, miR-10a prevents the Tregs differentiation into Th17 subset by targeting the transcriptional repressor Bcl-6 [40]. Examples of epigenetic regulations involving the T cell stability are: [44,45] Lower Treg-specific miR-10a expression has been found in mice with a genetic susceptibility for autoimmune diabetes [46].…”

Increased Osteopontin Levels in Children Undergoing Venom Immunotherapy May Serve as a Marker of Clinical Efficacy

“…Furthermore, OPN is reported to be associated with the regulation of allergic and fibrotic responses [22,23]. The possible association between OPN and asthma pathogenesis has also been determined in 2 studies on children [24,25]. To sum up, the data obtained from previous studies support the idea that OPN plays a key role as an effector cytokine involved in allergic inflammation.…”

A Novel Test for Detecting SNP–SNP Interactions in Case-Only Trio Studies

“…There has been a renewed interest in trio cohorts with affected offspring for the purposes of identifying de novo mutations and parent-of-origin effects (Arjomandi et al 2011;O'Roak et al 2011O'Roak et al , 2012Neale et al 2012;Sanders et al 2012). While these collections have identified many de novo mutations, they have not yet been examined for the presence of interactions and our test is therefore of immediate benefit to these rapidly growing trio cohorts.…”