Hedgehog-interacting protein ( HHIP ) polymorphisms and chronic obstructive pulmonary disease (COPD)

Genome wide association studies (GWAs) have identified single nucleotide polymorphisms (SNPs) in the region of Hedgehog interacting protein ( HHIP ) to be associated with COPD, level of lung function and height in the general population. We aim to investigate the association of rs1032295 and rs13147758 with lung function level and decline in subjects from the general population, as well as the association with lung function level and decline and small airways function in subjects with established COPD. Two SNPs rs1032295 and rs13147758 in the HHIP region were genotyped in 1,152 subjects from the general population (Doetinchem) and 110 COPD patients (GLUCOLD). Associations of the SNPs with lung function level and small airways function (FEV 1 and FEF25-75%) at baseline were analyzed using linear regression. For the longitudinal analyses of the same parameters we used linear mixed-effect models. Within smokers from the general population individuals homozygote for rs13147758 had a significantly higher FEV 1 level compared to wild-type individuals B (95%CI) = 163.4 ml (14.7-312.1). COPD patients heterozygote for rs13147758 had significantly smaller FEV 1 decline, i.e. 2.7 ml/yr (0.7-4.8) less decline, than wild-type individuals. None of the SNPs was significantly associated with FEF25-75% level or decline. This study suggests that rs13147758 in the HHIP region is associated with the maximum achieved lung function level in the general population but not with lung function decline. Moreover, SNPs in the HHIP region associated significantly with less lung function decline in individuals with established COPD patients, suggesting a possible protective effect of the gene in COPD patients.