title: Genetic polymorphisms associated with priapism in sickle cell disease.
abstract: 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 Sbeta(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-beta receptor, type III (TGFBR3) (rs7526590; P = 0.00058), aquaporin (AQP1) (rs10244884; P = 0.00068), integrin alphav (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 TGFbeta pathway, coagulation, cell adhesion and cell hydration pathways may be important in risk for priapism.
authors.affiliation: Department of Medicine, Duke University and VA Medical Centers, Durham, NC 27710, USA.
authors.forename: Laine
authors.initials: L
authors.lastname: Elliott
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
authors.forename: Laura
authors.initials: L
authors.lastname: De Castro
authors.forename: Jude
authors.initials: J
authors.lastname: Jonassaint
authors.forename: Jennifer
authors.initials: J
authors.lastname: Price
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Ataga
authors.forename: Marc C
authors.initials: MC
authors.lastname: Levesque
authors.forename: J
authors.initials: J
authors.lastname: Brice Weinberg
authors.forename: James R
authors.initials: JR
authors.lastname: Eckman
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Orringer
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Telen
mesh_terms: D000328:Adult; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000150:complications / Q000235:genetics*; D051398:Aquaporin 1 / Q000235:genetics; D005176:Factor XIII / Q000235:genetics; D006451:Hemoglobin, Sickle / Q000235:genetics; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics; D008297:Male; D009569:Nitric Oxide / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011317:Priapism / Q000150:complications / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D013789:Thalassemia / Q000235:genetics
chemical_list: D006451:Hemoglobin, Sickle; D039564:Integrin alphaV; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C064015:factor XIII subunit A; C071736:betaglycan; D051398:Aquaporin 1; D009569:Nitric Oxide; D005176:Factor XIII