Genetic variants in HHIP are associated with FEV1 in subjects with chronic obstructive pulmonary disease

Respirology. 2013 Nov;18(8):1202-9. doi: 10.1111/resp.12139.

Abstract

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 Caucasians, and additional studies in multiple ethnic groups are needed. We investigated genetic associations of HHIP in Korean 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 Soonchunhyang University Bucheon Hospital Biobank. Secondly, 219 individuals with COPD were recruited from the Korean Obstructive Lung Disease (KOLD) cohort. The control subjects consisted of 305 smokers or ex-smokers with normal lung function who were registered in the Korean Genome Epidemiology Study. 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 (FEV1 ) of these COPD subjects was 1.32 L. None of 15 SNP was significantly associated with COPD susceptibility. However, four SNP associated significantly with FEV1 in subjects with COPD. In the KOLD cohort study, two SNPs (rs11938704 and rs10013495) near HHIP were significantly associated with FEV1 (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.

Keywords: chronic obstructive pulmonary disease; genetic association analysis; hedgehog interacting protein; lung function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics*
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology
  • Case-Control Studies
  • Female
  • Forced Expiratory Volume / genetics*
  • Forced Expiratory Volume / physiology
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Linear Models
  • Lung / diagnostic imaging
  • Lung / physiopathology
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Pulmonary Disease, Chronic Obstructive / ethnology*
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Republic of Korea / epidemiology
  • Respiratory Function Tests
  • Smoking / adverse effects
  • Tomography, X-Ray Computed

Substances

  • Carrier Proteins
  • HHIP protein, human
  • Membrane Glycoproteins