Figure 4: Sex differences in erythrocyte phosphatidylinositol glycan class A (PIG-A ) mutant frequency for 5 publications. Solid bars represent the mean mutant frequency and error bars show standard deviation. The white numbers on each bar represent the number of healthy participants in each category.
As DNA damage and subsequent mutations can accumulate with age due to age-related reductions in DNA repair capacity and the lifelong accumulation of such DNA damage, the potential impact of age has been investigated by several research groups. A significant association between older age and increased mutant frequencies was found in three cohorts interrogating erythrocytes (Dertinger et al., 2015; Haboubi et al., 2019; Lawrence et al., 2020) and one interrogating reticulocytes (Torous et al., 2020), whilst other research groups either found minimal or no correlation with age. However, when Cao and colleagues measured the utility of this assay to identify mutagenicity in a cohort occupationally exposed to polycyclic aromatic hydrocarbons, the statistical analysis performed accounted for the impact of age on mutant frequency, suggesting there may be an age effect in this ethnic Chinese population (Cao et al., 2021). We may expect a correlation between mutation accumulation and age, with previous publications demonstrating an increased in single-base substitution mutational burden with age (Robinson et al., 2021). However, the studies published to date do not include a sufficient number of participants at either end of the age spectrum to fully inform us whether an effect exists on an epidemiological scale.