Novel genetic variants in long non-coding RNA MEG3 are associated with the risk of asthma

Kuo-Liang Chiu; Wen-Shin Chang; Chia-Wen Tsai; Mei-Chin Mong; Te-Chun Hsia; Da-Tian Bau

doi:10.7717/peerj.14760

Novel genetic variants in long non-coding RNA MEG3 are associated with the risk of asthma

PeerJ. 2023 Jan 27:11:e14760. doi: 10.7717/peerj.14760. eCollection 2023.

Authors

Kuo-Liang Chiu^{1

2}, Wen-Shin Chang^{3

4}, Chia-Wen Tsai^{3

4}, Mei-Chin Mong⁵, Te-Chun Hsia⁴, Da-Tian Bau^{3

4

6}

Affiliations

¹ Division of Chest Medicine, Department of Internal Medicine, Taichung Tzu Chi Hospital, Taichung, Taiwan.
² School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan.
³ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁴ Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
⁵ Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan.
⁶ Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.

Abstract

Background: Asthma is the most common chronic inflammatory airway disease worldwide. Asthma is a complex disease whose exact etiologic mechanisms remain elusive; however, it is increasingly evident that genetic factors play essential roles in the development of asthma. The purpose of this study is to identify novel genetic susceptibility loci for asthma in Taiwanese. We selected a well-studied long non-coding RNA (lncRNA), MEG3, which is involved in multiple cellular functions and whose expression has been associated with asthma. We hypothesize that genetic variants in MEG3 may influence the risk of asthma.

Methods: We genotyped four single nucleotide polymorphisms (SNPs) in MEG3, rs7158663, rs3087918, rs11160608, and rs4081134, in 198 patients with asthma and 453 healthy controls and measured serum MEG3 expression level in a subset of controls.

Results: The variant AG and AA genotypes of MEG3 rs7158663 were significantly over-represented in the patients compared to the controls (P = 0.0024). In logistic regression analyses, compared with the wild-type GG genotype, the heterozygous variant genotype (AG) was associated with a 1.62-fold [95% confidence interval (CI) [1.18-2.32], P = 0.0093] increased risk and the homozygous variant genotype (AA) conferred a 2.68-fold (95% CI [1.52-4.83], P = 0.003) increased risk of asthma. The allelic test showed the A allele was associated with a 1.63-fold increased risk of asthma (95% CI [1.25-2.07], P = 0.0004). The AG plus AA genotypes were also associated with severe symptoms (P = 0.0148). Furthermore, the AG and AA genotype carriers had lower serum MEG3 expression level than the GG genotype carriers, consistent with the reported downregulation of MEG3 in asthma patients.

Conclusion: MEG3 SNP rs7158663 is a genetic susceptibility locus for asthma in Taiwanese. Individuals carrying the variant genotypes have lower serum MEG3 level and are at increased risks of asthma and severe symptoms.

Keywords: Asthma; Genotype; MEG3; Polymorphism; Transcriptional expression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asthma* / genetics
Genetic Predisposition to Disease
Genotype
Humans
Polymorphism, Single Nucleotide
RNA, Long Noncoding* / genetics

Substances

RNA, Long Noncoding
MEG3 non-coding RNA, human

Grants and funding

This study was supported by grants from Taichung Tzu Chi Hospital (TTCRD111-15), China Medical University Hospital, and Asia University (CMU111-ASIA-02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.