Genetic variations in RORα are associated with chronic obstructive pulmonary disease.

Retinoic acid receptor-related orphan receptor-α (RORα) plays a key role in the regulation of lipid and cholesterol metabolism that has been implicated in the development of chronic obstructive pulmonary disease (COPD). The aim of this study was to determine the frequencies of single-nucleotide polymorphisms (SNPs) in RORα gene in a Chinese population and their possible association with COPD susceptibility. Nine tagging SNPs, including rs17270181, rs1898413, rs17270216, rs8033552, rs8036966, rs7169364, rs340002, rs340023 and rs11630262, were screened in 279 COPD patients and 367 controls by the SNaPshot method. Association analysis of genotypes and haplotypes constructed from these loci with COPD was conducted under different genetic models. Alleles or genotypes of rs8033552 distributed significantly differently in COPD patients and controls (allele: P=0.0001, false discovery rate (FDR) Q=0.004, odds ratios (OR): 1.62 and 95% confidence interval (CI): 1.27-2.07; genotype: P=0.0005, FDR Q=0.008). The allele A at rs8033552 was potentially associated with an increased risk of COPD in additive model, displaying ORs of 1.62 (95% CI: 1.17-2.26, P=0.004, FDR Q=0.019) in subjects with genotypes AG vs GG and 2.69 (95% CI: 1.47-4.93, P=0.001, FDR Q=0.011) in subjects with genotypes AA vs GG, respectively. In haplotype analysis, we observed haplotypes GGAGATGTG and GGAGCTGTG had protective effects, whereas haplotypes GGAGATACA and GGAGATACG were significantly associated with the increased risk of COPD. These data suggest that RORα may be a potential risk gene for COPD.