Significant Association of Cyclin D1 Promoter Genotypes With Asthma Susceptibility in Taiwan

Abstract

Background/Aim: The molecular mechanisms underlying the association between cell cycle and asthma are poorly understood, and cyclin D1 (CCND1) is found to be upregulated in asthma airway smooth muscle. We investigated whether the most frequently examined functional variants in CCND1 determine asthma susceptibility. Materials and Methods: We genotyped 651 participants for single-nucleotide polymorphisms (SNPs) at rs9344 and rs678653 on CCND1 and assessed the association of these SNPs with asthma risk. Results: Significant differences were found in the distributions of genotypic (p=0.0064) and allelic (p=0.0021) frequencies of CCND1 rs9344. In addition, AG or GG carriers had 0.63-or 0.48-fold adjusted odds ratios for asthma risk (95%confidence intervals=0.48-0.92 and 0.22-0.78, respectively) than those who carried the AA wildtype. Conclusion: Our results suggest that cell cycle regulation may play a role in asthma initiation and development, and the CCND1 rs9344 genotype may serve as an early detection marker for asthma.Asthma is a complex airway disease characterized by eosinophilic infiltration, airflow obstruction, mucus hypersecretion, goblet cell hyperplasia, and airway hyperresponsiveness and remodeling. According to a report by the World Allergy Organization, up to 300 million people suffer from asthma, and its prevalence continues to increase. Thus, asthma is a worldwide health problem (1). Clinically, asthmatic patients usually present with wheezing, cough, and dyspnea. Asthma has an estimated heritability higher than 60% (2, 3), but due to high immunological and phenotypical variations among asthmatic patients, asthma is considerably heterogeneous (4). Studies conducted in an animal disease model have suggested that approximately 200 genes are closely related to the etiology of asthma (5). Moreover, a multitude of environmental risk factors, including indoor and outdoor allergens, pollutants, smog, and air particles, may all contribute to higher risk of asthma. To date, a rather substantial body of evidence has documented typical structural alterations in the airways and lung parenchyma among asthmatic patients. These lines of evidence show that abnormal hypertrophy and hyperplasia of airway cells, such as goblet cells, smooth muscle cells, fibroblasts, and epithelial cells, take part in the processes of airway remodeling in asthma (6-10). At the molecular level, the proliferation of these human airway cells is controlled by cell cycle regulatory genes. It is possible that the genotypes of cell cycle regulatory genes may determine the personal 2041 This article is freely accessible online.

Molecular Mechanism of YuPingFeng in the Treatment of Asthma Based on Network Pharmacology and Molecular Docking Technology

“…The signal nucleotide polymorphism in CCND1 was linked with obesity [ 45 ]; meanwhile, it might participate in the process of asthma initiation and development [ 46 ]. PPARG is a central regulator in adipogenesis; PPARG-dependent transcription plays an essential role in regulating mitochondrial function [ 47 , 48 ].…”

Identification of miRNA–mRNA–TFs regulatory network and crucial pathways involved in asthma through advanced systems biology approaches

“…Moreover, an association of the CCND1 genotype with the asthma susceptibility has been observed [ 66 ]. These results suggest that hsa-miR-193b-3p may regulate asthma by regulating the cell cycle [ 67 ] ( Table 4 ).…”

Genetic variants in miR-145 gene are associated with the risk of asthma in Taiwan

“…One hundred and ninety-eight asthmatic cases were recruited at China Medical University Hospital in central Taiwan. Simultaneously, 453 non-asthmatic individuals matched by gender and age were enrolled as controls 10 . The study was approved and supervised by Research Ethics Committee of China Medical University Hospital (CMUH106-REC1-004), and performed in accordance with the Declaration of Helsinki.…”