Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease

Hum Mutat. 2006 Jan;27(1):103-9. doi: 10.1002/humu.20275.


Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. While cigarette smoking is a major cause of COPD, only 15% of smokers develop the disease, indicating major genetic influences. The most widely recognized candidate gene in COPD is SERPINA1, although it has been suggested that SERPINA3 may also play a role. To detect cryptic genetic variants that might contribute to disease, we identified 15 SNP haplotype tags from high-density SNP maps of the two genes and evaluated these SNPs in the largest case-control genetic study of COPD conducted so far. For SERPINA1, six newly identified haplotypes with a common backbone of five SNPs were found to increase the risk of disease by six- to 50-fold, the highest risk of COPD reported to date. In contrast, no haplotype associations for SERPINA3 were identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Case-Control Studies
  • Exons / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Haplotypes*
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Risk Factors
  • alpha 1-Antitrypsin / genetics*


  • SERPINA1 protein, human
  • alpha 1-Antitrypsin