Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype
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
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.
. Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype[J]. Frontiers of Medicine, 2013, 7(4): 425-432.
Xu Chen, Xiaomao Xu, Fei Xiao. Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype. Front Med, 2013, 7(4): 425-432.
Including age, gender, smoking history, ethnicity, etc.
Rapid decline in FEV1
A distinct phenotype; the rate may decrease after smoking cessation
Imaging phenotype
Lung structural abnormalities measured by CT or quantitative CT
AECOPD
More severe impairments and higher risks of hospitalization and death
Systemic inflammation
COPD is also an inflammatory response to noxious stimuli
Lymphatic vessels phenotype
Reflects the stages by the changes of distal lung immune cell traffic
Comorbidities
Chronic bronchitis, cardiovascular diseases, asthma, diabetes, etc.
Tab.1
Phenotype
Gene
Genotype
Function
Clinical
Smoking
ET-1[44]
198G/G
Higher incidence of COPD in smokers (-)
CHRNA3/5[45-50]
rs6495309 C/T& T/Trs8034191 C/C
Significantly decreased risk of COPD (+)Population attributable risk of 12.2% (-)
EPHX1[61]
H139R
Weakly protective, significant in Asian(+)
Physiological
FEV1
MMP12[53]
rs2276109 G/G
Reduced risk of the onset of COPD (+)
SOD3[54]
rs8192287 G/Trs8192288 G/T
Higher risk, reduced FEV1% predicted and FVC%predicted (-)
HHIP[55]
rs11938704rs10013495
Significantly associated with FEV1 in subjects with COPD
Imaging
Emphysema
SERPINA1[43]
PI Z/Z
Incidence:1% to 2%; Highest risk of COPD(-)
MMP-9[54]
-1562C/T
Alter promoter activity, increased risk (-)
Inflammation
IL6/IL6R[56]
rs4129267 C/T
Smoking induced inflammation (-)
IL1RN[58]
*2 Alleles
Strong risk of COPD in Asian females (-)
TNFA[56,57]
-308A allele
Risk for the development of COPD (-)
TNFB1[57]
rs2241712 A/G
Protective (+)
rs1982073 T/C
rs1800469 C/T
rs6957 A/G
Increased risk of COPD (-)
Tab.2
Fig.1
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