RESUMO
The complications of sickle cell disease are probably determined by genes whose products modify the pathophysiology initiated by the sickle haemoglobin mutation. Priapism, one vaso-occlusive manifestation of sickle cell disease, affects more than 30% of males with the disease. We examined the possible association of single nucleotide polymorphisms (SNPs) in 44 candidate genes of different functional classes for an association with the occurrence of priapism. One hundred and forty-eight patients with sickle cell anaemia and incident or a confirmed history of priapism were studied, along with 529 controls that had not developed priapism. Polymorphisms in the KLOTHO gene (KL; 13q12) showed an association with priapism by genotypic [reference SNP cluster identifier number (rs)2249358; odds ratio (OR) = 2.6 (1.4-5.5); rs211239; OR = 1.7 (1.2-2.6)] and haplotype analyses [rs211234 and rs211239; OR = 2.3 (1.5-3.4)]. These findings may have broader implications in sickle cell disease, as KL encodes a membrane protein that regulates many vascular functions, including vascular endothelial growth factor expression and endothelial nitric oxide release.
