Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease

✍ Scribed by Sally Chappell; Leslie Daly; Kevin Morgan; Tamar Guetta Baranes; Josep Roca; Roberto Rabinovich; Ann Millar; Seamas C. Donnelly; Vera Keatings; William MacNee; Jan Stolk; Pieter Hiemstra; Massimo Miniati; Simonetta Monti; Clare M. O'Connor; Noor Kalsheker

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 186 KB
• Volume: 27
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.20275

✦ Synopsis

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.