Genetic polymorphism in the cathepsin G gene and the risk of Alzheimer's disease

Alzheimer's disease (AD) is a complex disease with the possible involvement of several genes. The APOE*4 allele has been documented to be a major risk factor for sporadic late-onset AD, but it is neither necessary nor suffici ent to cause the disease. Cathepsin G, a serine protease found commonly in the azurophillic granules of neutrophils, has been reported to possess some beta -secretase like properties, and thus may be involved in the processin g of amyloid precursor protein (APP). Recently, an A -->G polymorphism has been reported in exon 4 of the cathepsin G gene, which changes the codon AA C ((125) Asp) to AGC ((125)Ser). In this study, we have investigated the as sociation of this polymorphism with sporadic late-onset AD. We screened DNA samples from 464 late-onset AD cases and 310 age-matched controls. No sign ificant association was seen between this polymorphism and AD. When the dat a were stratified by the APOE*4 carrier status, no significant difference w as seen either. Our data show no effect of this cathepsin G polymorphism in AD. Characterization of additional polymorphisms in this gene may provide more conclusive answers. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.