Analysis of the association of ANO3/MUC15, COL4A4, RRBP1, and KLK1 polymorphisms with COPD susceptibility in the Kashi population

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial, polygenic disease. The rate of occurrence of COPD in the Kashi population (Uyghur) is significantly higher than that observed nationwide. The identification of COPD-related genes in the Chinese Uyghur population could provide useful insights that could help us understand this phenomenon. Our previous whole-exome sequencing study of three Uyghur families with COPD demonstrated that 72 mutations in 55 genes might be associated with COPD; these included rs15783G > A in the anoctamin 3 (ANO3) gene/mucin 15 (MUC15) gene, rs1800517G > A in the collagen type IV alpha 4 chain (COL4A4) gene, rs11960G > A in the ribosome binding protein 1 (RRBP1) gene, and rs5516C > G in the kallikrein 1 (KLK1) gene. This case–control study aimed to further validate the association of the four mutations with COPD in the Chinese Uyghur population. METHODS: Sanger sequencing was used for the genotyping of four polymorphisms (ANO3/MUC15 rs15783, COL4A4 rs1800517, RRBP1 rs11960, and KLK1 rs5516) in 541 unrelated Uyghur COPD patients and 534 Uyghur healthy controls. We then conducted stratified analyses based on the smoking status and airflow limitation severity, to explore the correlation between selected gene polymorphisms and COPD. RESULTS: ANO3/MUC15 rs15783 and KLK1 rs5516 polymorphisms could significantly reduce COPD risk (p < 0.05), but COL4A4 rs1800517 and RRBP1 rs11960 polymorphisms were not correlated with COPD in the entire population. In a stratified analysis of smoking status, non-smokers with the ANO3/MUC15 rs15783G/G genotype (OR = 0.63, p = 0.032) or COL4A4 rs1800517 allele G (OR = 0.80, p = 0.023) had a reduced risk of COPD. Smokers with the RRBP1 rs11960A/G genotype had a lower risk of COPD (OR = 0.41, p = 0.025). The KLK1 rs5516G > C polymorphism was associated with a decreased risk of COPD (OR < 1, p < 0.05), irrespective of the smoking status of individuals. No significant association with COPD severity was observed in individuals with these four polymorphisms (p > 0.05). CONCLUSION: We identified four previously unreported mutations (ANO3/MUC15 rs15783, COL4A4 rs1800517, RRBP1 rs11960, and KLK1 rs5516) that might decrease the COPD risk in individuals with different smoking statuses in the Chinese Uyghur population. Our findings provide new light for the genetic risk factors associated with the occurrence of COPD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-022-01975-3.