Role of Genetic Polymorphisms in IL12Rβ2 in Chronic Obstructive Pulmonary Disease

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is the most common chronic inflammatory airway disease. Il-12r beta 2 (IL-12Rβ2) is important for the production of pathogenic Th1 cells. We aimed to explore the association between IL-12Rβ2 genetic variants and COPD risk among southern Chinese Han population.

Methods: We recruited 996 participants to perform an association analysis through SNPStats online software. We used false-positive report probability analysis to detect whether the positive findings were noteworthy. Haploview 4.2 software and SNPStats were used to conduct the haplotype analysis and linkage disequilibrium. Finally, the interaction of SNP-SNP in COPD risk was evaluated by multi-factor dimensionality reduction.

Results: The study found evidence that genetic loci in IL-12Rβ2 (rs2201584, rs1874791, rs6679356, and rs3790567) were potentially associated with the COPD susceptibility. In particular, IL-12Rβ2-rs2201584 and -rs1874791 showed close associations with COPD risk in both overall and several stratified analyses. Overall analysis or several stratified analyses indicated that allele A or homozygous genotype AA of IL-12Rβ2-rs2201584 were risk factors for COPD (Allele A: OR (95% CI) = 1.23 (1.02-1.48), p = 0.033; genotype AA: OR (95% CI) = 1.76 (1.15-2.69), p = 0.009). The allele A or homozygous genotype AA of IL-12Rβ2- rs1874791 were also risk factors for COPD (Allele A: OR (95% CI) = 1.36 (1.10-1.68), p = 0.004; genotype AA: OR (95% CI) = 2.17 (1.18-3.99), p = 0.013).

Conclusion: Intronic variants in IL-12Rβ2 (rs2201584, rs1874791, rs6679356, and rs3790567) were associated with the COPD susceptibility. In particular, there were sufficient evidences that IL-12Rβ2-rs2201584 and -rs1874791 were associated with the increasing risk of COPD.

Keywords: Chinese Han population; IL-12Rβ2; chronic obstructive pulmonary disease; genetic variants.

Figure 1

Flowchart for screening candidate SNPs.

Figure 2

One linkage disequilibrium block composed by the IL-12Rβ2 genetic loci (rs2201584 and rs1874791). The numbers inside the diamonds indicate The D’ for pairwise analyses.

Figure 3

Multifactor dimensionality reduction (MDR) analysis of interaction between the candidate genetic loci of IL-12Rβ2 (rs2201584, rs10489626, rs6659932, rs1874791, rs6679356, and rs3790567). SNP-SNP Interaction Dendrogram: the color represents the degree of redundancy or synergy between SNP-SNP; the closer the color is to red, the more synergy, and the closer to blue, the more redundancy.