Symptomatic stroke is a major complication of homozygous sickle cell (SS) disease, with a prevalence of approximately 10%. An elevated peripheral leukocyte count has been identified as a risk factor for hemorrhagic stroke in adults with SS disease. It has been observed that sickle cells coated with immunoglobulin have increased adherence to endothelial cells or phagocytes, possibly via binding to the low-affinity Fcgamma receptors. Common polymorphisms have been described in three low-affinity receptors: FCGR2A, FCGR3A, and FCGR3B; each has been shown to alter biological function, and each has also been associated with disease susceptibility. On the basis of this information, we evaluated common genetic variants of the low-affinity Fcgamma receptors for an association with symptomatic stroke in SS disease in a pilot case-control study of 51 Jamaican adult SS disease stroke cases and 51 SS disease-matched controls. Comparison of allelic distributions between cases and controls at 3 loci, FCGR2A (P = 0.39), FCGR3A (P = 0.67), FCGR3B (P = 0.35), failed to demonstrate a significant association. In a separate analysis, the FCGR2A/FCGR3A two-locus combination does not appear to segregate randomly (P(COR) = 0.0053), suggesting that these two loci could be linked in this population. We conclude that polymorphisms of the low-affinity Fcgamma receptors are not associated with stroke in SS disease.
Published 2002 Wiley-Liss, Inc.