Objectives: This study investigates whether genetic modifiers previously shown to influence adult fetal hemoglobin (HbF) levels and glucose-6-phosphate dehydrogenase deficiency were associated with variable symptomology in a small sample of collegiate football players with sickle cell trait.
Methods: Survey data on self-assessed symptoms and genotype data from five single nucleotide polymorphisms (SNPs) related to HbF production and two SNPs that cause glucose-6-phosphate dehydrogenase deficiency were collected from current and former college football players.
Results: In this sample, SNPs found within the β-globin gene cluster were found to be associated with a previous diagnosis of exertional sickling and experience of extreme heat during and after training. rs10189857 in the BCL11A gene was associated with body mass index and weight and with experiencing extreme thirst during and after training. No significant correlations were found between the other SNPs and symptoms within this sample.
Conclusions: These findings show that genetic variation known to affect sickle cell disease symptomology may partly explain why some football players with sickle cell trait experience adverse clinical outcomes during periods of extreme physical exertion and others do not.