Yi-ming Yuan1, Jin-long Zhang2, Si-cheng Xu3, Ren-song Ye4, Dan Xu2, You Zhang2, Yan-Jie Zhang2, Yu-long Chen2, Yu-lan Liu2, Zhi-guang Su2. 1. Department of Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China. 2. Molecular Medicine Research Center, West China Hospital, and State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China. 3. Respiratory Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China. 4. Department of Internal Medicine, The Affiliated Shanghai Eighth People's Hospital of Jiangsu University, Shanghai 200235, China.
Abstract
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 (OR=0.42, P=0.023) and in the dominant model at rs12922394 (OR=0.70, 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<0.05). 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.
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 COPDpatients 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 COPDpatients 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 (OR=0.42, P=0.023) and in the dominant model at rs12922394 (OR=0.70, 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<0.05). 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.
Authors: Ying Wu; Yun Li; Ethan M Lange; Damien C Croteau-Chonka; Christopher W Kuzawa; Thomas W McDade; Li Qin; Ghenadie Curocichin; Judith B Borja; Leslie A Lange; Linda S Adair; Karen L Mohlke Journal: Hum Mol Genet Date: 2010-09-27 Impact factor: 6.150
Authors: Ming Zhu; Christopher Hug; David I Kasahara; Richard A Johnston; Alison S Williams; Norah G Verbout; Huiqing Si; Jordan Jastrab; Amit Srivastava; Erin S Williams; Barbara Ranscht; Stephanie A Shore Journal: Am J Respir Cell Mol Biol Date: 2009-11-13 Impact factor: 6.914
Authors: Xiuqing Guo; Mohammed F Saad; Carl D Langefeld; Adrienne H Williams; Jinrui Cui; Kent D Taylor; Jill M Norris; Sujata Jinagouda; Christine H Darwin; Braxton D Mitchell; Richard N Bergman; Beth Sutton; Y-D Ida Chen; Lynne E Wagenknecht; Donald W Bowden; Jerome I Rotter Journal: Diabetes Date: 2006-06 Impact factor: 9.461
Authors: Jian-Qing He; John E Connett; Nicholas R Anthonisen; Peter D Paré; Andrew J Sandford Journal: Am J Respir Crit Care Med Date: 2004-06-07 Impact factor: 21.405
Authors: Christopher Hug; Jin Wang; Naina Shehzeen Ahmad; Jonathan S Bogan; Tsu-Shuen Tsao; Harvey F Lodish Journal: Proc Natl Acad Sci U S A Date: 2004-06-21 Impact factor: 11.205