Genetic Variants in the Hedgehog Interacting Protein Gene Are Associated with the FEV1/FVC Ratio in Southern Han Chinese Subjects with Chronic Obstructive Pulmonary Disease.

Zili Zhang,Kai Yang,Lian Dong,Xindong Chen,Defu Li,Ning Lai,Yi Zhang,Wenju Lu,Jiaze Shu,Zeguang Zheng,Jian Wang,Xiansheng Zeng

doi:10.1155/2017/2756726

Abstract

Background Convincing evidences have demonstrated the associations between HHIP and FAM13a polymorphisms and COPD in non-Asian populations. Here genetic variants in HHIP and FAM13a were investigated in Southern Han Chinese COPD. Methods A case-control study was conducted, including 989 cases and 999 controls. The associations between SNPs genotypes and COPD were performed by a logistic regression model; for SNPs and COPD-related phenotypes such as lung function, COPD severity, pack-year of smoking, and smoking status, a linear regression model was employed. Effects of risk alleles, genotypes, and haplotypes of the 3 significant SNPs in the HHIP gene on FEV1/FVC were also assessed in a linear regression model in COPD. Results The mean FEV1/FVC% value was 46.8 in combined COPD population. None of the 8 selected SNPs apparently related to COPD susceptibility. However, three SNPs (rs12509311, rs13118928, and rs182859) in HHIP were associated significantly with the FEV1/FVC% (Pmax = 4.1 × 10−4) in COPD adjusting for gender, age, and smoking pack-years. Moreover, statistical significance between risk alleles and the FEV1/FVC% (P = 2.3 × 10−4), risk genotypes, and the FEV1/FVC% (P = 3.5 × 10−4) was also observed in COPD. Conclusions Genetic variants in HHIP were related with FEV1/FVC in COPD. Significant relationships between risk alleles and risk genotypes and FEV1/FVC in COPD were also identified.

Highlights

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease characterized by airflow limitation that is not completely reversible
Kim et al found that, in the KOLD cohort study, two SNPs near HHIP were significantly associated with FEV1 (P = 0.0001 and 0.001, resp.) in COPD [28]
In the current case-control study, we explored the role of multiple variants of FAM13a and HHIP and assessed their relationships with COPD, and with COPDrelated phenotypes in above described Southern Chinese Han population

Summary

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease characterized by airflow limitation that is not completely reversible. Tobacco smoking was suggested to be the major adverse factor for the progress of COPD, about 85% of the smokers did not develop into clinically relevant airflow obstruction [3], implying that genetic susceptibility might play a crucial role in the development of COPD. Genome-wide association studies (GWAS), which have revolutionized the identification of susceptibility genes for polygenic diseases, figured out statistically significant relations regarding the FAM13a and HHIP and COPD in nonAsian populations [5,6,7,8]. The genetic relationships between the FAM13a and HHIP genes and COPD were conducted by the Southern Han Chinese COPD case-control study.

Methods

Results

Conclusion