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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (4) : 425-432
Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype
Xu Chen1, Xiaomao Xu2, Fei Xiao1()
1. Key Laboratory of Geriatrics, Beijing Institute of Geriatrics; 2. Department of Respiratory Medicine, Beijing Hospital, Ministry of Health, Beijing 100730, China
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Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality throughout the world and is mainly characterized by persistent airflow limitation. Given that multiple systems other than the lung can be impaired in COPD patients, the traditional FEV1/FVC ratio shows many limitations in COPD diagnosis and assessment. Certain heterogeneities are found in terms of clinical manifestations, physiology, imaging findings, and inflammatory reactions in COPD patients; thus, phenotyping can provide effective information for the prognosis and treatment. However, phenotypes are often based on symptoms or pathophysiological impairments in late-stage COPD, and the role of phenotypes in COPD prevention and early diagnosis remains unclear. This shortcoming may be overcome by the potential genotypes defined by the heterogeneities in certain genes. This review briefly describes the heterogeneity of COPD, with focus on recent advances in the correlations between genotypes and phenotypes. The potential roles of these genotypes and phenotypes in the molecular mechanisms and management of COPD are also elucidated.

Keywords chronic obstructive pulmonary disease      heterogeneity      phenotype      genotype      prediction     
Corresponding Author(s): Xiao Fei,   
Issue Date: 05 December 2013
 Cite this article:   
Xu Chen,Xiaomao Xu,Fei Xiao. Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype[J]. Front Med, 2013, 7(4): 425-432.
Clinical phenotypeIncluding age, gender, smoking history, ethnicity, etc.
Rapid decline in FEV1A distinct phenotype; the rate may decrease after smoking cessation
Imaging phenotypeLung structural abnormalities measured by CT or quantitative CT
AECOPDMore severe impairments and higher risks of hospitalization and death
Systemic inflammationCOPD is also an inflammatory response to noxious stimuli
Lymphatic vessels phenotypeReflects the stages by the changes of distal lung immune cell traffic
ComorbiditiesChronic bronchitis, cardiovascular diseases, asthma, diabetes, etc.
Tab.1  Phenotypes of COPD
SmokingET-1[44]198G/GHigher incidence of COPD in smokers (-)
CHRNA3/5[45-50]rs6495309 C/T& T/Trs8034191 C/CSignificantly decreased risk of COPD (+)Population attributable risk of 12.2% (-)
EPHX1[61]H139RWeakly protective, significant in Asian(+)
FEV1MMP12[53]rs2276109 G/GReduced risk of the onset of COPD (+)
SOD3[54]rs8192287 G/Trs8192288 G/THigher risk, reduced FEV1% predicted and FVC%predicted (-)
HHIP[55]rs11938704rs10013495Significantly associated with FEV1 in subjects with COPD
EmphysemaSERPINA1[43]PI Z/ZIncidence:1% to 2%; Highest risk of COPD(-)
MMP-9[54]-1562C/TAlter promoter activity, increased risk (-)
IL6/IL6R[56]rs4129267 C/TSmoking induced inflammation (-)
IL1RN[58]*2 AllelesStrong risk of COPD in Asian females (-)
TNFA[56,57]-308A alleleRisk for the development of COPD (-)
TNFB1[57]rs2241712 A/GProtective (+)
rs1982073 T/C
rs1800469 C/T
rs6957 A/GIncreased risk of COPD (-)
Tab.2  Correlations between the phenotypes and genotypes of COPD
Fig.1  Interactions among different COPD factors
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