Background. Asthma is a common complex disease, associated with chronic inflammation in the airways. Etiology and mechanisms remain elusive. It is known that genetic factors play important roles in the development of asthma. The purpose of this study is to identify if there were novel genetic susceptibility loci for asthma in Taiwanese. The long non-coding RNA, MEG3, is known to be involved in multiple cellular functions and associated with asthma. We hypothesize that genetic variants in MEG3 may be associated with the risk of asthma. 

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

Results. The variant AG and AA genotypes of MEG3 rs7158663 were significantly overrepresented in the patients, compared to the controls (P = 0.0024). The heterozygous variant genotype (AG) was associated with a 1.62-fold (P= 0.0093) increased risk, compared with the wild-type GG genotype, and the homozygous variant genotype (AA) conferred a 2.68-fold (P = 0.003) increased risk of asthma. The A allele was associated with a 1.63-fold increased risk of asthma (P = 0.0004). The AG plus AA genotypes were also associated with worse symptoms (P = 0.0148). Moreover, compared with the GG genotype carriers, the AG and AA genotype carriers had lower serum MEG3 expression level.

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