Association of Interleukin-12A rs568408 with Susceptibility to Asthma in Taiwan

Te-Chun Shen,Wei-Chun Chen,Shengyu Wang,Wen-Shin Chang,Chieh-Lun Hsiao,Te-Chun Hsia,Chia-Wen Tsai,Che-Yi Chao,Da-Tian Bau

doi:10.1038/s41598-017-03523-0

Abstract

Asthma is an inflammatory disease and interleukin 12 (IL-12) may play a regulatory role in allergen-induced inflammation. The aim of this study was to investigate the association of polymorphisms in IL-12A/IL-12B with asthma. The asthma group included 198 adult patients and the control group included 453 individuals without asthma that were frequency-matched by gender and age. The distribution of genotypic and allelic frequencies of IL-12A rs568408 demonstrated significant differences between case and control groups. Specifically, the percentages of AA genotype of IL-12A rs568408 was significantly higher among asthmatic patients in Taiwan than healthy controls, compared to GG genotype. No significant difference was observed among the IL-12A rs2243115 and IL-12B rs3212227 genotypes between case and control groups. In addition, the A allele at IL-12A rs568408 was associated with more severe symptoms (P = 0.0085) among asthmatic patients. These results suggest that IL-12A rs568408 may contribute to the etiology and symptoms severity of asthma, indicating its usefulness as a predictive and diagnostic biomarker of asthma.

Highlights

Cytokines play a pivotal role in regulation of the immune responses and the polymorphic nature of cytokine genes may confer flexibility of cellular immune phenomenum[10]
There was a significant difference in the distribution of IL-12A rs568408 genotypes between cases and control groups (P = 0.0041), but not for those of IL-12A rs2243115 and IL-12B rs3212227
The AA genotype [odds ratio (OR) = 3.50, 95% confidence interval (CI) = 1.57–7.82, P = 0.0022], but not AG (OR = 1.28, 95% CI = 0.86–1.91, P = 0.2175), at IL-12A rs568408 demonstrated a statistically significant risk for asthma in Controls Cases (N = 198) (N = 453)

Summary

Introduction

Cytokines play a pivotal role in regulation of the immune responses and the polymorphic nature of cytokine genes may confer flexibility of cellular immune phenomenum[10]. IL-12 impairs neo-angiogenesis in tumor tissues through induction of IFN-γ-inducible protein-10 (IP-10)[14] Because of these pleiotropic activities, IL-12 is regarded as one of the most feasible cytokines to be applied as immunotherapy for neoplasms[16]. In 2011, Chen and colleagues reported that IL-12A rs568408 and IL-12B rs3212227 SNPs may individually and jointly contribute to asthma risk in a moderate population, 197 asthma patients and 369 controls in mainland China[23]. This is the first paper to examine the contribution of IL-12 genotypes to asthma susceptibility without any further analysis of clinical features or outcomes. In the current study, IL-12A rs568408, IL-12A rs2243115, and IL-12B rs3212227 polymorphisms were selected to investigate the associated risk of asthma in Taiwan, and their associations with clinical features, such as symptoms severity

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