Association of genetic polymorphisms with chronic obstructive pulmonary disease in the Chinese Han population: a case–control study

BMC Medical Genomics

Huanying Wan⁵  Zhihong Jiang⁵  Liang Fan⁵  Ting Cheng⁵  Yi Chen³  Qiuling Weng¹  Lei Ren¹  Qingyun Li⁵  Qijian Cheng⁵  Guochao Shi⁵  Yanrong Qian⁵  Chunming Pan⁴  Yi Gong²  Yi Guo⁵ 

[1] Department of Respiratory Medicine, Shanghai Jing-an geriatric Hospital, 200042, Shanghai, China;Department of Respiratory Medicine, Hua Shan Hospital, Fu Dan University, 200040, Shanghai, China;Department of Respiratory Medicine, Shanghai Gong Hui Hospital, 200041, Shanghai, China;State Key Laboratory of Medical Genomics, Molecular Medicine Center, Shanghai Rui Jin Hospital, 200025, Shanghai, China;Department of Pulmonary Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 200025, Shanghai, China

关键词: Allele frequencies;    Genotype;    Single-nucleotide polymorphisms;    COPD;   

Others  :  1121231
DOI  :  10.1186/1755-8794-5-64

 received in 2012-08-22, accepted in 2012-12-13,  发布年份 2012

【 摘 要 】

Background

Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. Few gene studies of the Chinese population have focused on COPD. We investigated candidate genes associated with susceptibility to COPD in the Chinese Han population.

Methods

A total of 331 COPD patients and 213 control subjects were recruited for this study. Nighty-seven single-nucleotide polymorphisms (SNPs) of 46 genes were selected for genotyping. Genotypes were determined using multiplex polymerase chain reaction (PCR).

Results

Significant differences between patients and healthy controls were observed in the allele frequencies of seven SNPs: rs1205 C, rs2353397 C, rs20541 T, rs2070600 G, rs10947233 G, rs1800629 G, and rs2241712 A. After Bonferroni correction, rs2353397 C was most strongly associated with susceptibility to COPD. Haplotype analysis showed that the frequencies of the GC, GT haplotypes of rs2241718 (TGF-β1 gene), and rs6957 (CDC97 gene) were significantly higher in the control group than in the COPD case group (p=1.88×10^-9); the frequencies of the TT haplotype of rs1205 and rs2808630 (CRP gene) were significantly higher in the control group (p=0.0377).

Conclusion

Our study suggests some genetic variants associated with the susceptibility of COPD in the Chinese Han population.

【 授权许可】

   
2012 Guo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Rabe KF, Beghé B, Luppi F, Fabbri LM: Update in chronic obstructive pulmonary disease 2006. Am J Respir Crit Care Med 2007, 175(12):1222-1232.
• [2]Murray CJL, Lopez AD: Evidence-based health policy: lessons from the global burden of disease study. Science 1996, 274(5288):740-743.
• [3]Silverman EK: Progress in chronic obstructive pulmonary disease genetics. Proc Am Thorac Soc 2006, 3(5):405-408.
• [4]Lokke A, Lange P, Scharling H, Fabricius P, Vestbo J: Developing COPD: a 25-year follow up study of the general population. Thorax 2006, 61(11):935-939.
• [5]Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K: Environmental and heritable factors in the causation of cancer: analyses of cohorts of twins from Sweden, Denmark and Finland. N Eng J Med 2000, 343(2):78-85.
• [6]McCloskey SC, Patel BD, Hinchliffe SJ, Reid ED, Wareham NJ, Lomas DA: Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med 2001, 164(8):1419-1424.
• [7]Chen Y: Genetics and pulmonary medicine.10: Genetic epidemiology of pulmonary function. Thorax 1999, 54(9):818-824.
• [8]Wilk JB, Chen TH, Gottlieb DJ, Walter RE, Nagle MW, Brandler BJ, Myers RH, Borecki IB, Silverman EK, Weiss ST, O’Connor GT: A genome-wide association study of pulmonary function measures in the Framingham Heart Study. PLoS Genet 2009, 5(3):e1000429.
• [9]Pillai SG, Ge DL, Zhu GH, Kong XY, Shianna KV, Need AC, Feng S, Hersh CP, Bakke P, Gulsvik A, Ruppert A, Lødrup Carlsen KC, Roses A, Anderson W, Investigators ICGN, Rennard SI, Lomas DA, Silverman EK, Goldstein DB: A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet 2009, 5(3):e1000421.
• [10]Hancock DB, Eijgelsheim M, Wilk JB, Gharib SA, Loehr LR, Marciante KD, Franceschini N, van Durme YMTA, Chen TH, Barr RG, Schabath MB, Couper DJ, Brusselle GG, Psaty BM, van Duijn CM, Rotter JI, Uitterlinden AG, Hofman A, Punjabi NM, Rivadeneira F, Morrison AC, Enright PL, North KE, Heckbert SR, Lumley T, Stricker BHC, O’Connor GT, London SJ: Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet 2010, 42(1):45-52.
• [11]Cho MH, Boutaoui N, Klanderman BJ, Sylvia JS, Ziniti JP, Hersh CP, et al.: Variants in FAM13A are associated with chronic obstructive pulmonary disease. Nat Genet 2010, 42(3):200-202.
• [12]Repapi E, Sayers I, Wain LV, Burton PR, Johnson T, Obeidat M, et al.: Genome-wide association study indentifies five loci associated with lung function. Nat Genet 2010, 42(1):36-44.
• [13]Tomashefski JF Jr, Crystal RG, Wiedemann HP, Mascha E, Stoller JK: The bronchopulmonary pathology of alpha-1 antitrypsin (AAT) deficiency: findings of the Death Review Committee of the national registry for individuals with Severe Deficiency of Alpha-1 Antitrypsin. Hum Pathol 2004, 35(12):1452-1461.
• [14]Wang XY, Li L, Xiao JL, Jin CZ, Huang K, Kang XW, Wu XM, Lv FZ: Association of ADAM33 gene polymorphisms with COPD in a northeastern Chinese population. BMC Medical Genetics 2009, 10:132-138. BioMed Central Full Text
• [15]Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, Weel CV, Zielinski J: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007, 176(6):532-555.
• [16]Edwards MC, Gibbs RA: Multiplex PCR: advantages, development, and applications. Genome Res 1994, 3(5):S65-75.
• [17]Kayed H, Kleeff J, Keleg S, Guo J, Ketterer K, Berberat PO, Giese N, Esposito I, Giese T, Büchler MW, Friess H: Indian hedgehog signaling pathway:expression and regulation in pancreatic cancer. Int J Cancer 2004, 110(5):668-676.
• [18]Villavicencio EH, Walterhouse DO, Iannaccone PM: The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet 2000, 67(5):1047-1054.
• [19]Zhou XB, Baron RM, Hardin M, Cho MH, Zielinski J, Hawrylkiewicz I, Sliwinski P, Hersh CP, Mancini JD, Lu K, Thibault D, Donahue AL, Klanderman BJ, Rosner B, Raby BA, Lu Q, Geldart AM, Layne MD, Perrella MA, Weiss ST, Choi AMK, Silverman EK: Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP. Hum Mol Genet 2012, 21(6):1325-1335.
• [20]Lemjabbar-Alaoui H, Dasari V, Sidhu SS, Mengistab A, Finkbeiner W, Gallup M, Basbaum C: Wnt and hedgehog are critical mediators of cigarette smoke-induced lung cancer. PLoS One 2006, 1:e93.
• [21]Sakao S, Tatsumi K, Igari H, Watanabe R, Shino Y, Shirasawa H, Kuriyama T: FCCP Association of tumor necrosis factor gene promoter polymorphism with low attenuation areas on high-resolution CT in patients with COPD. Chest 2002, 122(2):416-420.
• [22]Keicho N, Emi M, Nakata K, Taguchi Y, Azuma A, Tokunaga K, Ohishi N, Kudoh S: Promoter variation of tumour necrosis factor-alpha gene:possible high risk for chronic bronchitis but not diffuse panbronchiolitis. Respir Med 1999, 93(10):752-753.
• [23]Stankovic MM, Nestorovic AR, Tomovic AM, Petrovic-Stanojevic ND, Andjelicjelic A, Dopudja-Pantic VB, Nagorni-Obradovic LM, Mitic-Milikic MM, Radojkovic DP: TNF-alpha-308 promotor polymorphism in patients with chronic obstructive pulmonary disease and lung cancer. Neoplasma 2009, 56(4):348-352.
• [24]Papatheodorou A, Latsi P, Vrettou C, Dimakou A, Chroneou A, Makrythanasis P, Kaliakatsos M, Orfanidou D, Roussos C, Kanavakis E, Tzetis M: Development of a novel microarray methodology for the study of SNPs in the promoter region of the TNF-alpha gene:their association with obstructive pulmonary disease in Greek patients. Clin Biochem 2007, 40(12):843-850.
• [25]Chung KF: Cytokines in chronic obstructive pulmonary disease. Eur Respir J 2001, 18(Suppl 34):50s-59s.
• [26]Bouma G, Crusius JBA, Pool MO, Kolkman JJ, von Blomberg BME, Kostense PJ, Giphart MJ, Schreuder GMTH, Meuwissen SGM, Peña AS: Secretion of tumor necrosis factor α and lymphotoxin in relation to polymorphisms in TNF genes and HLA-DR alleles: relevance for inflammatory bowel disease. Scand J Immunol 1996, 43(4):456-463.
• [27]Moffatt MF, Cookson OCM: Tumor necrosis factor haplotypes and asthma. Hum Mol Genet 1997, 6(4):551-554.
• [28]Su ZG, Wen FQ, Feng YL, Xiao M, Wu XL: Transforming growth factor-beta1 gene polymorphisms associated with chronic obstructive pulmonary disease in Chinese population. Acta pharmacol sin 2005, 26(6):714-720.
• [29]Van Diemen CC, Postma DS, Aulchenko YS, Snijders PJLM, Oostra BA, van Duijin CM, Boezen M: Novel strategy to identify genetic risk factors for COPD severity: a genetic isolate. Eur Respir J 2010, 35(4):768-775.
• [30]Silverman ES, Palmer LJ, Subramaniam V, Hallock A, Mathew S, Vallone J, Faffe DS, Shikanai T, Raby BA, Weiss ST, Shore SA: Transforming Growth Factor-β1 promoter polymorphism C-509T is associated with asthma. AM J Respir Crit Care Med 2004, 169(2):214-219.
• [31]Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, Carter ND, Spector TD: Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 1999, 8(1):93-97.
• [32]Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ Jr, Chapman HA Jr, Shapiro SD, Elias JA: Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest 2000, 106(9):1081-1093.
• [33]Miotto D, Ruggieri MP, Boschetto P, Cavallesco G, Papi A, Bononi I, Piola C, Murer B, Fabbri LM, Mapp CE: Interleukin-13 and −4 expression in the central airways of smokers with chronic bronchitis. Eur Respir J 2003, 22(4):602-608.
• [34]Beghé B, Hall IP, Parker SG, Moffatt MF, Wardlaw A, Connolly MJ, Fabbri LM, Ruse C, Sayers I: Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease. Allergy 2010, 65(4):474-481.
• [35]Black S, Teixeira AS, Loh AXW, Vinall L, Holloway JW, Hardy R, Swallow DM: Contribution of functional variation in the IL13 gene to allergy, hay fever and asthma in the NSHD longitudinal 1946 birth cohort. Allergy 2009, 64(8):1172-1178.
• [36]Sunyer J, Pistelli R, Plana E, Andreani M, Baldari F, Kolz M, Koenig W, Pekkanen J, Peters A, Forastiere F: Systemic inflammation, genetic susceptibility and lung function. Eur Respir J 2008, 32(1):92-97.
• [37]Kardys I, de Maat MP, Uitterlinden AG, Hofman A, Witteman JC: C-reactive protein gene haplotypes and risk of coronary heart disease: the Rotterdam Study. Eur Heart J 2006, 27(11):1331-1337.
• [38]Pinto-Plata VM, Müllerova H, Toso JF, Feudjo-Tepie M, Soriano JB, Vessey RS, Celli BR: C-reactive protein in patients with COPD, control smokers and nonsmokers. Thorax 2006, 61(1):23-28.
• [39]Castaldi PJ, Cho MH, Litonjua AA, Bakke P, Gulsvik A, Lomas DA, Anderson W, Beaty TH, Hokanson JE, Crapo JD, Laird N, Silverman EK, COPD Gene and Eclipse investigators: The association of genome-wide significant spirometric loci with chronic obstructive pulmonary disease susceptibility. AM J Respir Cell Mol Biol 2011, 45(6):1147-1153.
• [40]Hardin M, Zielinski J, Wan ES, Hersh CP, Castaldi PJ, Schwinder E, Hawrylkiewicz I, Sliwinski P, Cho MH, Silverman EK: CHRNA3/5, IREB2, and ADCY2 are associated with severe COPD in Poland. Am J Respir Cell Mol Biol 2012, 47(2):203-208.