This study was a literature review conducted to understand the genetic variations and how they contribute to different degrees of severity of sickle cell disease (SCD), as seen specifically in the Indian subcontinent. The study was also driven by the fact that although SCD was among the first monogenic disorders to be discovered, the complexity of its genetic pathophysiology is yet to be understood. The non-globin genes modifying the clinical presentation of SCD specific to the Indian cohort were identified and compared to the non-Indian cohorts. An advanced PubMed search was done using the keywords “sickle cell disease” AND “genetics” AND “India,” yielding 300 hits. Out of these articles, those regarding genes affecting the pathophysiology of SCD were filtered manually. Through the comprehensive review that followed, it was observed based on the data reviewed that subjects with SCD having mutations of the Factor V Leiden gene and methylenetetrahydrofolate reductase C677T polymorphisms were prone to vascular complications, which were linked to lower levels of protein C and higher amounts of procoagulants like prothrombin fragments (F1 + 2), D-dimer, and thrombin-antithrombin. Another significant discovery was an association of the endothelial nitric oxide synthase ( eNOS ) gene polymorphism as a potential genetic modifier, potentially causing vaso-occlusive crisis and BCL11A, with an increased level of fetal hemoglobin (HbF) in the Indian population. Increases in HbF levels were also associated with the XMN1 gene in patients with SCD and thalassemia . This study was significant as it laid more emphasis on genes that influenced sickling of the red blood cells, and hence tried to identify genes that were specific to complications in the Indian population. It also drew our attention to the fact that studies conducted so far have factored in a relatively small sample size, and there is a need for a more comprehensive review in a larger sample size, with a need to consider other factors such as diet and climate, which can influence the disease pathophysiology in various subgroups of the Indian population.
Chhabra et al. (Sat,) studied this question.