PPARA Gene Polymorphisms and Their Association with COPD in Tibetan and Han Populations from Gansu, China

Int J Chron Obstruct Pulmon Dis. 2026 May 16:21:590361. doi: 10.2147/COPD.S590361. eCollection 2026.

Abstract

Background: Chronic Obstructive Pulmonary Disease (COPD) is influenced by both genetic and environmental factors, with chronic hypoxia playing a pivotal role in its pathogenesis. Peroxisome proliferator-activated receptor alpha (PPARA), a core regulator of the hypoxia pathway, exhibits genetic differentiation in high-altitude populations. This study aimed to investigate the association between PPARA gene polymorphisms and COPD susceptibility in Tibetan and Han populations in Gansu Province.

Methods: A case-control study design was employed. A total of 1276 participants (399 Tibetans and 877 Han Chinese) were recruited from Gansu province. Using Haploview software, four tag SNPs of the PPARA gene (rs135538, rs135539, rs135549, rs4253758) were selected. Genotyping was performed using the iMLDR (Improved Multiple Ligase Detection Reaction) multiplex SNP genotyping technique.

Results: In the Tibetan population, the rs135539A>C polymorphism under a dominant model was associated with an increased risk of COPD (CC+CA vs. AA: OR = 1.779, 95% CI: 1.080-2.903, P=0.024). In the Han population, rs135549T>C under a dominant model was associated with a reduced COPD risk (CC+CT vs. TT: OR = 0.719, 95% CI: 0.547-0.944, P = 0.017). The rs4253758T>C SNP exhibited a dual effect in Han Chinese: under an additive model, both TC (OR = 1.722, 95% CI: 1.504-2.813, P = 0.030) and CC (OR = 1.778, 95% CI: 1.083-2.922, P = 0.023) genotypes increased risk compared to the TT genotype. However, under a recessive model, the CC genotype was protective compared to TT+TC (OR = 0.572, 95% CI: 0.356-0.918, P = 0.021). No significant associations were found for other SNPs.

Conclusion: PPARA gene polymorphisms are associated with COPD susceptibility in a population-specific manner among Tibetan and Han populations in Gansu. The rs135539A>C variant increases COPD risk in Tibetans, whereas rs135549T>C and rs4253758T>C exert protective and dual effects, respectively, in the Han population.

Keywords: PPARA; chronic obstructive pulmonary disease; ethnicity; single nucleotide polymorphism.

MeSH terms

  • Aged
  • Asian People* / genetics
  • Case-Control Studies
  • Chi-Square Distribution
  • China / epidemiology
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • PPAR alpha* / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / ethnology
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Risk Factors
  • Tibet / epidemiology

Substances

  • PPARA protein, human
  • PPAR alpha