Disease Severity and Genetic Variability in pregnant women with Sickle Cell Disease

July 11, 2024

Sickle cell disease (SCD) is a genetic disorder caused by a mutation in the HBB gene of adult hemoglobin, which is highly prevalent in sub-Saharan Africa. This disease displays a high degree of clinical variability and severity, influenced by genetic factors such as α-thalassemia and fetal hemoglobin levels modifiers. Recent advancements in care have improved life expectancy for SCD patients, consequently increasing the number of pregnancies among SCD patients. This change underscores the need to better understand the disease's impact on pregnancy and the modulatory effects of genetic factors. This thesis evaluates the severity of SCD and pregnancy outcomes in 125 Angolan patients, focusing on the effects of the 3.7kb α-thalassemia deletion, βS-haplotypes, and polymorphisms in the BCL11A and HIC2 genes. Through association studies, the relationships between these genetic modifiers and clinical outcomes, laboratory parameters, and pregnancy results were analyzed both individually and combined into a genetic score. Findings suggest that α-thalassemia inheritance and the absence of at least one CAR allele improve laboratory indices, reduce certain SCD complications, and enhance pregnancy outcomes. Other polymorphisms showed effects on laboratory variables but did not improve the disease phenotype. The genetic score analysis did not yield results significantly different from the individual genetic modifiers. Overall, this research highlights the intricate role of genetic factors in influencing SCD severity and pregnancy outcomes, advocating for more extensive studies to further understand these dynamics and develop tailored management strategies for SCD in pregnant women.

Authors in the community:

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  C

  Carolina Paiva Lopes Frazão Cruz

  ist192801

Supervisors of this institution:

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  S

  Susana de Almeida Mendes Vinga Martins

  ist14109

industrial-biotechnology - Industrial Biotechnology

eng - English

Instituto Superior Técnico