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Genetic polymorphisms associated with priapism in sickle cell disease
Author(s) -
Elliott Laine,
AshleyKoch Allison E.,
Castro Laura De,
Jonassaint Jude,
Price Jennifer,
Ataga Kenneth I.,
Levesque Marc C.,
Brice Weinberg J.,
Eckman James R.,
Orringer Eugene P.,
Vance Jeffery M.,
Telen Marilyn J.
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06560.x
Subject(s) - priapism , single nucleotide polymorphism , candidate gene , immunology , medicine , biology , genetic association , allele , genetics , bioinformatics , gene , genotype , psychiatry
Summary Priapism occurs in 30–45% of male patients with sickle cell disease (SCD), but the possible influence of genetic risk factors on the incidence of priapism is not well understood. We examined genetic polymorphisms in 199 unrelated, adult (>18 years), male patients with Hb SS and Hb S β 0 ‐thalassaemia, 83 (42%) of whom reported a history of priapism. Candidate genes for association with priapism were identified based on their involvement in adhesion, coagulation, inflammation and cell signalling. Additionally, we examined genes involved in nitric oxide biology ( NOS2, NOS3, SLC4A1 ), as well as polymorphisms in the klotho ( KL ) gene, which has previously been associated with priapism. Strong evidence of association was found for single nucleotide polymorphisms in transforming growth factor‐ β receptor, type III ( TGFBR3 ) (rs7526590; P = 0·00058), aquaporin ( AQP1 ) (rs10244884; P = 0·00068), integrin α v ( ITGAV ) (rs3768780; P = 0·00090), and the A1 subunit of coagulation factor XIII ( F13A1 ) (hcv1860621; P = 0·00156). Associations with TGFBR3 , AQP1 , and ITGAV remained significant after adjusting for multiple testing, using the Benjamini–Hochberg procedure. Our data suggest that genes involved in the TGF β pathway, coagulation, cell adhesion and cell hydration pathways may be important in risk for priapism.