Individuals who carry two copies of the Δ32 mutation of the CCR5 gene (which protects against HIV infection in Europeans) have a 21% increase in mortality rate, according to a study published in Nature Medicine this week. The results highlight the need to better understand how the unintended consequences of introducing mutations in humans may impact health.
In 2018, Jiankui He announced that he had used CRISPR to edit the CCR5 gene in human embryos, which resulted in two live births. The introduced mutations were aimed at mimicking the effect of the naturally occurring CCR5-Δ32 mutation. However, previous studies have also suggested that people with this mutation may be at risk for certain infectious diseases, such as influenza.
Xinzhu Wei and Rasmus Nielsen analysed genotype and death register information for over 400,000 individuals in the UK Biobank to investigate the effect of the Δ32 mutation on life expectancy. The authors found that individuals who are homozygous carriers of the Δ32 mutation (Δ32/Δ32) are about 20% less likely to reach age 76, compared to those who do not have or only have one copy of the Δ32 mutation. They also found that the number of Δ32/Δ32 individuals at the time of enrollment in the UK Biobank cohort is lower than expected, consistent with the notion of a harmful effect of Δ32 in the homozygous state. It remains to be seen if these findings can be replicated in other populations.