Interaction Between Self-Reported Environmental Sensitivity and Genetic Protective Factors in Sickle Cell Anemia
DOI:
https://doi.org/10.47363/JCET/2026(7)151Keywords:
Sickle Cell, Fetal Hemoglobin, Α-Thalassemia, Latent Class Analysis, Gene-Environment InteractionAbstract
Background: Sickle Cell Anemia (SCA) is characterized by heterogeneous clinical presentations, partly explained by endogenous fetal hemoglobin (HbF) and α-thalassemia co-inheritance. Environmental exposures may modify these genetic protective effects. We examined whether self-reported environmental sensitivity modifies the association of HbF and α-thalassemia with disease severity in patients with SCA in Yaoundé, Cameroon.
Methods: In this cross-sectional, multicenter study, 125 patients aged ≥5 years with confirmed hemoglobin SS genotype were recruited from five healthcare facilities in the Centre region of Cameroon. Participants completed a questionnaire assessing self-reported sensitivity to cold, humidity, wind, dust, smoke, and seasonal vaso-occlusive crisis (VOC) patterns. Latent class analysis (LCA) was used to identify subgroups with similar environmental sensitivity profiles. We tested interactions between latent class, HbF, and the α-thalassemia 3.7 kb deletion on pain episode frequency and hospitalization rates using bias-reduced regression models.
Results: Two latent classes were identified based on their conditional probabilities. Latent Class 1 (18.4%, n=23) was characterized by high sensitivity to dust, smoke, and year-round VOC risk. Latent Class 2 (81.6%, n=102) was characterized by sensitivity to cold, wind, and humid conditions with rainy-season VOC peaks. The protective effect of HbF on pain frequency (IRR 1.17, 95% CI 1.02–1.34) and hospitalization (IRR 1.12, 95% CI 1.01–1.24) differed significantly by latent class, as did the protective effect of the α-thalassemia 3.7 kb deletion on hospitalization (IRR 0.29, 95% CI 0.10–0.89).
Conclusion: The clinical benefits of HbF and α-thalassemia co-inheritance in SCA are moderated by environmental sensitivity. These findings support gene-environment interaction among SCA patients in Cameroon and support individualized care that incorporates environmental risk profiling into routine standard practice.
