Association of Metabolic and DNA-repair gene polymorphisms with Longevity: a role for GSTT1, GSTP and XPC genes.

Abstract

Aging and longevity are complex processes controlled at different levels, including genetic level. We evaluated the association of seven drug and DNA-repair gene polymorphisms with longevity in an Italian cohort. A sample of 756 subjects aged 18-98 was genotyped for CYP1A1 exon 7 A>G, GSTT1 null, GSTM1 null, GSTP A>G, XRCC1 exon 6 C>T, XRCC1 exon 9 A> G and XPC exon 15 A>C gene polymorphisms. The association between the analyzed gene polymorphisms and longevity was evaluated by dividing the sample into three age groups: 10-50, 51-85, and 86-98. We observed a significant decrease in the frequency of the GSTT1 null, GSTP G and XPC C alleles in the oldest group with respect to the youngest one and with respect to 51-85 age group. We obtained the same results also subdividing the sample into 1-85 and 86-98 age groups. The general linear model analyses confirmed a significant decreasing trend of the above mentioned alleles with age. We hypothesized that these minor alleles, being important in the sensitivity against the development of different types of cancer, may reflect a reduced life-expectancy in carrier subjects and may explain their significantly lower frequency observed among subjects belonging to oldest age group.