Factors that influence PIG-A mutant frequency
Several human PIG-A studies have also looked to identify
individual factors that may result in mutant frequency variation. The
fact that humans have higher PIG-A mutant frequencies compared to
laboratory rodents (Olsen et al., 2017) could be due the fact that
humans are long-lived and are exposed to a wider range of lifestyle
genotoxins compared to laboratory confined rodents. Some of the human
studies mentioned above explored whether mutant frequency differs
between sexes, producing contrasting results (Figure 4). Dobrovolsky and
colleagues found that females had significantly higher erythrocyte
mutant frequencies compared to males (p=0.025), although only 26 females
were included in this cohort (Dobrovolsky et al., 2011). Conversely, Cao
and colleagues measured higher mutant erythrocytes in males compared to
females (p<0.0001) (Cao et al., 2016). The other publications
presented in Figure 2 (Cao, Wang, Xi, et al., 2020; Cao et al., 2021;
Haboubi et al., 2019; Lawrence et al., 2020) as well as the study by
Dertinger and colleagues (Dertinger et al., 2015) (not shown in Figure
4) revealed no significant differences in erythrocyte PIG-Amutant frequencies between sexes. A study measuring reticulocytePIG-A identified a higher level of mutant reticulocytes in males
compared to females (Torous et al., 2020). Even though the reason behind
these sex differences is unclear it may be due to the different
ethnicities studied in these particular two groups with one research
group measuring PIG-A mutation status in an ethnic Chinese
population (Cao et al., 2016) and the other in a mainly
Caucasian/Hispanic population (Dobrovolsky et al., 2011).This suggested
difference in gender may also be due to limited sample sizes and lack of
integration of alternative factors (known or unknown) that can confound
mutation status at the PIG-A locus.