Genetic variants of CDH13 determine the susceptibility to chronic obstructive pulmonary disease in a Chinese population

• Published in: Acta pharmacologica Sinica Vol. 37; no. 3; pp. 390 - 397
• Main Authors: Yuan, Yi-ming, Zhang, Jin-long, Xu, Si-cheng, Ye, Ren-song, Xu, Dan, Zhang, You, Zhang, Yan-Jie, Chen, Yu-long, Liu, Yu-lan, Su, Zhi-guang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2016; Nature Publishing Group
• Subjects: Adiponectin - blood; Aged; Asian Continental Ancestry Group - genetics; Biomedical and Life Sciences; Biomedicine; Cadherins - genetics; China - epidemiology; COPD; Female; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Immunology; Internal Medicine; Linkage Disequilibrium; Lung - metabolism; Lung - physiopathology; Male; Medical Microbiology; Middle Aged; Original; original-article; Pharmacology/Toxicology; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - epidemiology; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - physiopathology; Vaccine; 中国人口; 单核苷酸多态性; 基因变异; 基因型频率; 慢性阻塞性肺疾病; 慢性阻塞性肺病; 易感性; adiponectin; haplotype; Chinese individuals; biomarker; genetic polymorphism; chronic obstructive pulmonary disease
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1038/aps.2015.158

Aim： Adiponectin has been implicated in the development of chronic obstructive pulmonary disease （COPD）. The CDH13 gene encodes T-cadherin that is an adiponectin receptor, and genetic variants of CDH13 determine blood adiponectin levels. The aim of this study was to investigate the effects of CDH13 variants on COPD susceptibility in a Chinese population. Methods： Ten single-nucleotide polymorphisms （SNP） in CDH13 were screened using the SNaPshot method in 279 COPD patients and 367 control subjects. Association of genotypes or haplotypes constructed from these loci with COPD was analyzed in different genetic models.Results： Among the 10 SNPs tested, rs4783244 and rs12922394 exhibited significant differences in allele or genotype frequencies between COPD patients and control subjects, whereas 8 other SNPs did not. The minor allele T was associated with decreased risk of COPD in the recessive model at rs4783244 （0R=0.42, P=0.023） and in the dominant model at rs12922394 （OR=O.70, P=0.022）. The genotype TT at either rs4783244 or rs12922394 was associated with a significantly low level of plasma adiponectin when compared to genotypes GG and CC （P〈O.05）. Haplotypes GC in block 1 （rs4783244-rs12922394） as well as GTAC and ATGT in block 3 （rs4783266-rs11640522-rs11646849-rs11860282） significantly increased the risk of COPD, whereas haplotypes TT in block 1, TG in block 2 （rs11646011- rs11640875） and ATGC in block 3 were protective against COPD. Conclusion： CDH13 genetic variants determine Chinese individuals＇ susceptibility to COPD and thus are efficient genetic biomarkers for early detection of COPD.