Minjing Li1, Wanru Cai1, Ye Chen1, Lei Dong1. 1. Department of Pneumology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Abstract
Aims: Caveolin-1, which is encoded by the caveolin-1 (CAV1) gene, plays an important role in the development of pulmonary hypertension (PH). The purpose of this study was to determine the relationship between 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) of the CAV1 gene and the risk of PH in Chinese Han patients with chronic obstructive pulmonary disease (COPD). Methods: From March 2016 to October 2018, 235 patients with COPD combined with PH (COPD/PH+) and 240 patients with COPD and without PH (COPD/PH-) were recruited to the study. The CAV1 gene rs1049314, rs8713, rs1049334, rs6867, and rs1049337 loci were genotyped and the plasma hsa-miR-451 and caveolin-1 levels were measured in all subjects. Results: The risk of PH in patients with COPD carrying the C allele of the rs8713 locus was 2.82 times higher than that in A allele carriers (95% confidence interval [CI], 1.94-4.08; p < 0.001). The risk of PH in patients with COPD carrying the T allele of the rs1049337 locus was significantly lower than that in C allele carriers (odds ratio [OR], 0.48; 95% CI, 0.37-0.63; p < 0.001). The ACGAC haplotype was found to be a highly-significant risk factor for COPD combined with PH (OR, 2.24; 95% CI, 1.20-4.17; p = 0.01). Plasma levels of hsa-miR-451 and the caveolin1 protein in patients with the rs8713 C allele were significantly lower than in those with the wild type (WT) allele regardless of PH status. Conversely, the hsa-miRN-451 and caveolin-1 levels in patients with the rs1049337 mutant C allele were significantly higher than those in the WT T allele (p < 0.05). There was a positive correlation between plasma hsa-miR-451 and caveolin-1 levels in patients with COPD/PH+ and COPD/PH- (r = 0.72 and 0.63, respectively). Conclusion: SNPs of the CAV1 gene loci rs8713 and rs1049337 are associated with a risk of PH in COPD patients. The underlying mechanism is likely to be related to the effect of the SNPs on the regulation of caveolin-1 by hsa-miR-451.
Aims: Caveolin-1, which is encoded by the caveolin-1 (CAV1) gene, plays an important role in the development of pulmonary hypertension (PH). The purpose of this study was to determine the relationship between 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) of the CAV1 gene and the risk of PH in Chinese Han patients with chronic obstructive pulmonary disease (COPD). Methods: From March 2016 to October 2018, 235 patients with COPD combined with PH (COPD/PH+) and 240 patients with COPD and without PH (COPD/PH-) were recruited to the study. The CAV1 gene rs1049314, rs8713, rs1049334, rs6867, and rs1049337 loci were genotyped and the plasma hsa-miR-451 and caveolin-1 levels were measured in all subjects. Results: The risk of PH in patients with COPD carrying the C allele of the rs8713 locus was 2.82 times higher than that in A allele carriers (95% confidence interval [CI], 1.94-4.08; p < 0.001). The risk of PH in patients with COPD carrying the T allele of the rs1049337 locus was significantly lower than that in C allele carriers (odds ratio [OR], 0.48; 95% CI, 0.37-0.63; p < 0.001). The ACGAC haplotype was found to be a highly-significant risk factor for COPD combined with PH (OR, 2.24; 95% CI, 1.20-4.17; p = 0.01). Plasma levels of hsa-miR-451 and the caveolin1 protein in patients with the rs8713 C allele were significantly lower than in those with the wild type (WT) allele regardless of PH status. Conversely, the hsa-miRN-451 and caveolin-1 levels in patients with the rs1049337 mutant C allele were significantly higher than those in the WT T allele (p < 0.05). There was a positive correlation between plasma hsa-miR-451 and caveolin-1 levels in patients with COPD/PH+ and COPD/PH- (r = 0.72 and 0.63, respectively). Conclusion: SNPs of the CAV1 gene loci rs8713 and rs1049337 are associated with a risk of PH in COPDpatients. The underlying mechanism is likely to be related to the effect of the SNPs on the regulation of caveolin-1 by hsa-miR-451.