Association between PTCH1 gene polymorphisms and chronic obstructive pulmonary disease susceptibility in a Chinese Han population: a case-control study

Chin Med J (Engl). 2020 Sep 5;133(17):2071-2077. doi: 10.1097/CM9.0000000000000858.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the PTCH1 gene encoding Patched1, a receptor in the Hedgehog signaling pathway important for lung morphogenesis and pulmonary function. The aim of this study was to investigate the association between PTCH1 polymorphisms and the COPD risk in the Chinese Han population.

Methods: We performed a case-control study including 296 patients with COPD and 300 healthy individuals. Single-nucleotide polymorphisms in the PTCH1 gene were identified and genotyped based on the linkage disequilibrium analysis in all participants. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis after adjustment for age, gender, and smoking.

Results: In total, 28 single-nucleotide polymorphisms were identified in patients with COPD. Among them, "A" allele of rs28491365 (OR: 1.388, 95% CI: 1.055-1.827, P = 0.018), and "G" alleles of rs10512248 (OR: 1.299, 95% CI: 1.021-1.653, P = 0.033) and rs28705285 (OR: 1.359, 95% CI: 1.024-1.803, P = 0.033; respectively) were significantly associated with an increased COPD risk. Genetic model analysis revealed that the "T/T" genotype of rs34695652 was associated with a decreased COPD risk under the recessive model (OR: 0.490, 95% CI: 0.270-0.880, P = 0.010), whereas rs28504650/rs10512248 haplotype CG was significantly associated with an increased COPD risk after adjustment for age, gender, and smoking status (OR: 6.364, 95% CI: 1.220-33.292, P = 0.028).

Conclusions: The study provides a new insight into the role of PTCH1 polymorphisms in the susceptibility to COPD in the Chinese Han population.

MeSH terms

  • Asian People / genetics
  • Case-Control Studies
  • China
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study*
  • Genotype
  • Hedgehog Proteins
  • Humans
  • Patched-1 Receptor* / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Pulmonary Disease, Chronic Obstructive* / genetics

Substances

  • Hedgehog Proteins
  • PTCH1 protein, human
  • Patched-1 Receptor