Reduced cyclin D3 expression in erythroid cells protects against malaria - PubMed
4 days ago
- #erythrocyte biology
- #cyclin D3
- #malaria resistance
- Reduced cyclin D3 expression in erythroid cells is linked to protection against malaria.
- The variant rs112233623-T affects erythrocyte properties, increasing hemoglobin A2 levels, erythrocyte size, and reducing erythrocyte count.
- This variant disrupts a SMAD3 binding site in an erythroid enhancer of CCND3, leading to reduced cyclin D3 expression and inhibited cell-cycle progression in erythroblasts.
- Population genetic evidence suggests positive selection for rs112233623-T in Sardinia, historically a malaria-endemic region.
- Parasite growth is impaired in erythrocytes from rs112233623-T carriers, correlating with reactive oxygen species (ROS) levels, similar to G6PD deficiency's protective effect against malaria.
- The findings suggest targeting cyclin D3 reduction as a potential therapeutic strategy for malaria resistance.