Association of the rs7216389 Polymorphism in Orosomucoid-Like 3 (ORMDL3) Gene With Childhood Asthma: A Multicenter Case-Control Study.

Background Asthma is recognized worldwide as the most common chronic illness in children, and numerous environmental and genetic factors have been identified in its pathophysiology. Among genetic contributors, the orosomucoid-like 3 (ORMDL3) gene, a negative regulator of sphingolipid synthesis, has gained particular importance and has been significantly linked to the onset of asthma. This proposed connection highlighted the importance of comprehensive in vivo analysis and exploration of the effect of ORMDL3 on asthma immunopathology. The present study aimed to analyze and compare the distribution pattern of the ORMDL3 gene among children with and without asthma in order to evaluate its association with childhood asthma susceptibility. Methods This multicenter study, with a case-control design, was conducted across three institutes, namely, CMH Lahore Medical and Dental College, the University of Health Sciences, and the Children's Hospital Lahore, from March 3, 2021, to May 21, 2022. In this study, 50 asthmatic and 50 non-asthmatic children were enrolled, with participants ranging in age from three to 18 years and having a confirmed diagnosis of genetic asthma. For analysis of genotypic distribution and associations, the genomic DNA was first extracted and quantified using gel electrophoresis. Single-nucleotide polymorphism (SNP) genotyping was then performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Genotypic associations were then analyzed, with focus on rs7216389, with the C-allele considered more common in healthy individuals and the T-allele more frequent in asthmatic children.  Results With respect to the primary objective, analysis of the ORMDL3 rs7216389 polymorphism in our study found the heterozygous T/C genotype to be the most frequent among the asthmatic patients (n=34; 68%), and there was no significant observable difference between the genotype of asthmatic and non-asthmatic children. Altogether, a statistically significant association was not identified between the rs7216389 polymorphism and asthma status. In addition, seasonal fluctuations significantly (p<0.001) influenced asthma symptoms, with the majority proportion of asthmatic patients (n=30; 60%) reporting an exacerbation of symptoms with seasonal changes. Similarly, asthma symptoms were significantly exacerbated by animal and dust allergens, with p-values of 0.010 and 0.018, respectively.  Conclusion In conclusion, no association was found between the ORMDL3 rs7216389 polymorphism and childhood asthma in our study. These findings suggest that this variant is unlikely to serve as an independent predictor of asthma in children. Future research with a larger sample size, a diverse population, and a wider genomic analysis is recommended to better understand the genetic architecture of childhood asthma and to determine whether an association exists.