A longitudinal study of the effect of GSTT1 and GSTM1 gene copy number on survival

Deletions of the glutathione S-transferase superfamily genes GSTT1 and GSTM1 has been associated with oxidative stress related diseases and recently explored as factors implicated in longevity as well. Reported results have been conflicting, which may partially be caused by the traditional use of assays unable to discriminate between carriers of one or two functional genes. Using a quantitative realtime PCR method facilitating quantification of gene copy number, we evaluated the influence of GSTT1 and GSTM1 gene deletions on longevity in a longitudinal study of 681 elderly Danish twins. The mean follow-up time was 7.6 years and during this time a total of 294 deaths occurred. The results demonstrated a non-significant trend for carriage of two copies of the GSTM1 functional gene to be a protective factor, whereas both heterozygosity and homozygosity for the GSTT1 functional gene was associated with a moderate but significant increased mortality in women (hazard rate 2.46 (CI95: 1.43-4.23) and 2.22 (CI95: 1.25-3.94) for one and two alleles, respectively). To our knowledge, this is the first longitudinal study exploring the influence of GST gene polymorphisms on longevity and these data implies that GST gene copy numbers do affect mortality risk in the elderly.