Genetic variants in HHIP are associated with FEV 1 in subjects with chronic obstructive pulmonary disease

Background and objective  Chronic obstructive pulmonary disease ( COPD ) is a complex disease in which multiple genes and their interaction with environmental factors contribute to disease development. Recent genome‐wide association studies in COPD revealed the chromosome 4 region near hedgehog interacting protein ( HHIP ). However, these studies were mostly performed in C aucasians, and additional studies in multiple ethnic groups are needed. We investigated genetic associations of HHIP in K orean COPD and control subjects. Methods  Two separate case–control studies were performed. Firstly, 139 subjects with COPD and 199 control subjects were selected from the S oonchunhyang U niversity B ucheon H ospital B iobank. Secondly, 219 individuals with COPD were recruited from the K orean O bstructive L ung D isease ( KOLD ) cohort. The control subjects consisted of 305 smokers or ex‐smokers with normal lung function who were registered in the K orean G enome E pidemiology S tudy. Associations between COPD susceptibility and single‐nucleotide polymorphism ( SNP ) genotypes were tested by logistic regression. Associations between lung function and SNP genotypes were tested by linear regression. Results  In the first study, the mean forced expiratory volume in 1 s ( FEV 1 ) of these COPD subjects was 1.32 L. None of 15 SNP was significantly associated with COPD susceptibility. However, four SNP associated significantly with FEV 1 in subjects with COPD . In the KOLD cohort study, two SNP s (rs11938704 and rs10013495) near HHIP were significantly associated with FEV 1 ( P  = 0.0001 and 0.001, respectively) in subjects with COPD . Conclusions  Genetic variants in HHIP are associated with lung function in subjects with COPD .