Protease inhibitor phenotypes and serum alpha-1-antitrypsin levels in patients with COPD: a study from Hong Kong.
OBJECTIVE
Many studies have suggested that an imbalance of protease activation and inhibition might result in COPD with emphysema. Levels of alpha-1-antitrypsin (alpha1-AT), the key protease inhibitor, are genetically determined by alleles that present in many phenotypes/subtypes, some of which are associated with deficiency of the protein. We prospectively evaluated the prevalence of the protease inhibitor (Pi) alleles and phenotypes together with the serum alpha1-AT levels in Chinese patients with COPD.


METHODS
The study population comprised 356 patients with COPD. The male-to-female ratio was 4 : 1 with a mean age of 72.4 years (range 44-93 years). Isoelectric focusing was used for Pi phenotyping/subtyping. The frequencies of Pi alleles and phenotypes were compared with the frequencies in 1085 healthy unrelated Chinese control subjects. The serum alpha1-AT levels were measured by the Cobas Fara assay.


RESULTS
PiZ was not detected. No significant difference in distribution of PiM phenotypes/subtypes between patients with COPD and healthy controls was observed, except for M1M3 and M2M3. There was also a significant difference in the proportion of variant S and F alleles between the disease group and the control population.


CONCLUSIONS
The low prevalence of deficiency Pi phenotypes/subtypes suggests a lack of contribution of alpha1-AT deficiency to the pathogenesis of COPD in Chinese patients. The strategy of launching an alpha1-AT deficiency detection program among COPD patients, based on the recommendation of the World Health Organization, may not be readily applicable in our local setting.
Kwok
Janette S Y
JS
Department of Pathology, Queen Mary Hospital, Hong Kong, China.
Lawton
John W M
JW
Yew
Wing Wai
WW
Chau
Chi Hung
CH
Lee
Joseph
J
Wong
Poon Chuen
PC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000097:blood*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D000515:alpha 1-Antitrypsin / Q000032:analysis*
D011480:Protease Inhibitors; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin