Sequence variants of the secreted phosphoprotein 1 gene are associated with total serum immunoglobulin E levels in a Japanese population

Background: Secreted phosphoprotein 1 (SPP1) is a cytokine with pleiotrophic immunological activities, including activation of macrophage chemotaxis and T-helper type 1 (Th1) immune responses. SPP1 gene polymorphisms have been shown to be associated with several immune inflammatory diseases including multiple sclerosis (MS), which is characterized by fewer allergic symptoms and lower numbers of allergen sensitizations. Objective: The present study examined whether SPP1 gene polymorphisms are associated with total serum IgE levels, atopy and asthma in a Japanese population. Methods: This case-control association analysis examined 611 subjects, including 268 subjects with asthma. We genotyped three promoter and two exon polymorphisms at SPP1: -1687A/G; -381T/C; -94 deletion/G; 5891C/T; and 7052T/C. Results: Association analyses of SPP1 polymorphisms showed that homozygosities for the 5891T allele (P=0.009) and 7052C allele (P=0.001) were significantly associated with increased levels of total IgE in non-asthmatic subjects. However, these variants were not associated with asthma and atopy. Interestingly, individuals carrying the 5891C allele, which is more prevalent in patients with MS in Japanese populations, displayed significantly lower levels of total serum IgE. Individuals homozygous for the 7052C allele, which is associated with development of systemic lupus erythematosus, displayed significantly higher total serum IgE levels. Conclusion: These findings suggest that genetic polymorphisms in SPP1 may play a role in controlling basal levels of total serum IgE, independent of atopy.