GARP Polymorphisms Associated with Susceptibility to House Dust Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population

Abstract

Background

Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese.

Methods

In this hospital-based case–control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold.

Results

rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted OR = 1.393, 95% CI = 1.019–1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted OR = 0.646, 95% CI = 0.427–0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥16 years (adjusted OR = 1.745, 95% CI = 1.103–2.760), and this high risk was also found in the females (adjusted OR = 1.708, 95% CI = 1.021–2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted OR = 0.819, 95% CI = 0.676–0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699.

Conclusion

SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans.

Keywords:

• allergic rhinitis
• mites
• GARP
• LRRC32
• single nucleotide polymorphism
• genetic association studies

Abbreviations

AR, allergic rhinitis; ARIA, Allergic Rhinitis and its Impact on Asthma; CHB, Han Chinese in Beijing; CIs, confidence intervals; Der f, Dermatophagoides farinae; Der p, Dermatophagoides pteronyssinus; eQTL, expression quantitative trait locus; GARP, glycoprotein A repetitions predominant; GRASP, Genome-Wide Repository of Associations Between SNPs and Phenotypes; HWE, Hardy-Weinberg equilibrium; IgE, Immunoglobulin E; LD, linkage disequilibrium; LRRC32, leucine-rich repeat containing 32; MAF, minor allele frequency; MFE, minimum free energy; ORs, odds ratios; PER, persistent allergic rhinitis; SNPs, single nucleotide polymorphisms; TGF-β, transforming growth factor-β; Treg, regulatory T lymphocytes; UTR, untranslated region; VAS, visual analogue scale.

Ethics Approval and Informed Consent

The research protocol was approved by the Ethics Committee of Nanjing Medical University (20080305), and written informed consent was obtained from all participants.

Consent for Publication

We have obtained the informed consent from all patients or their legal guardians.

Acknowledgments

We are grateful to the participants in this study and all staff involved in the study through the years. We also thank associate professor Yong-Ke Cao at the College of Foreign Languages of Nanjing Medical University for professional English-language proofreading of the manuscript.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas. All authors took part in drafting, revising, or critically reviewing the article; have agreed on the journal to which the article has been submitted; gave final approval for the version to be published; and agreed to be accountable for the contents of the article.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by grants from the Health Promotion Project of Jiangsu Province (XK200719) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (JX10231801), People’s Republic of China.