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 Sβ0- 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 αv (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 TGFβ pathway, coagulation, cell adhesion and cell hydration pathways may be important in risk for priapism.
| Original language | English |
|---|---|
| Pages (from-to) | 262-267 |
| Number of pages | 6 |
| Journal | British Journal of Haematology |
| Volume | 137 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 1 2007 |
| Externally published | Yes |
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Keywords
- ITGAV
- Priapism
- Sickle cell
- Single nucleotide polymorphisms
- TGFBR3
ASJC Scopus subject areas
- Hematology
Cite this
Genetic polymorphisms associated with priapism in sickle cell disease. / Elliott, Laine; Ashley-Koch, 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.
In: British Journal of Haematology, Vol. 137, No. 3, 01.05.2007, p. 262-267.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic polymorphisms associated with priapism in sickle cell disease
AU - Elliott, Laine
AU - Ashley-Koch, Allison E.
AU - Castro, Laura De
AU - Jonassaint, Jude
AU - Price, Jennifer
AU - Ataga, Kenneth I.
AU - Levesque, Marc C.
AU - Brice Weinberg, J.
AU - Eckman, James R.
AU - Orringer, Eugene P.
AU - Vance, Jeffery M
AU - Telen, Marilyn J.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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 Sβ0- 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 αv (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 TGFβ pathway, coagulation, cell adhesion and cell hydration pathways may be important in risk for priapism.
AB - 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 Sβ0- 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 αv (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 TGFβ pathway, coagulation, cell adhesion and cell hydration pathways may be important in risk for priapism.
KW - ITGAV
KW - Priapism
KW - Sickle cell
KW - Single nucleotide polymorphisms
KW - TGFBR3
UR - http://www.scopus.com/inward/record.url?scp=34047205100&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047205100&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2007.06560.x
DO - 10.1111/j.1365-2141.2007.06560.x
M3 - Article
C2 - 17408468
AN - SCOPUS:34047205100
VL - 137
SP - 262
EP - 267
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 3
ER -