Abstract
Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected, for further studies, 7 polymorphisms located ≤ 2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure-associated polymorphisms identified in the previous studies. In conclusion, we have ide...Continue Reading
References
Dec 1, 1966·The Journal of Clinical Investigation·E G BiglieriN Brust
Nov 30, 1968·Nature·B S McEwenL S Schwartz
May 18, 2001·Endocrinology·A M KarssenE R de Kloet
Dec 21, 2002·Lancet·Sarah LewingtonUNKNOWN Prospective Studies Collaboration
Jun 27, 2003·Lancet·Mark CaulfieldUNKNOWN MRC British Genetics of Hypertension Study
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
Mar 19, 2005·Endocrinology·Walter L Miller
Dec 13, 2005·Molecular and Cellular Endocrinology·Kamalesh K SharmaStefan Andersson
Jul 5, 2006·Clinical Endocrinology·Peter J RaubenheimerJonathan R Seckl
Nov 1, 2006·Hypertension·Marianne BarrEleanor Davies
Jul 27, 2007·Clinical Endocrinology·E M FreelJ M C Connell
May 12, 2009·Nature Genetics·Daniel LevyCornelia M van Duijn
May 12, 2009·Nature Genetics·Christopher Newton-ChehPatricia B Munroe
Jun 9, 2009·Best Practice & Research. Clinical Endocrinology & Metabolism·Nils Krone, Wiebke Arlt
Apr 24, 2010·Journal of Human Genetics·Kyung-Won HongBermseok Oh
Sep 21, 2010·Journal of Hypertension·Chen LiuXu Lin
Nov 6, 2010·Endocrine Reviews·Walter L Miller, Richard J Auchus
Sep 13, 2011·Nature·UNKNOWN International Consortium for Blood Pressure Genome-Wide Association StudiesToby Johnson
Oct 4, 2011·Atherosclerosis·Yinghua LinGang Chen
Jun 2, 2012·Circulation Research·Frances McManusJohn M Connell
Sep 11, 2012·Metabolism: Clinical and Experimental·Bo XiJie Mi
Jul 7, 2015·Steroids·David J Morris
Aug 13, 2015·International Journal of Molecular Sciences·Matthias HuberReinhold Kreutz
Citations
Sep 30, 2016·Nature·Momoko HorikoshiRachel M Freathy
Feb 16, 2017·American Journal of Hypertension·Annemarie ReinoldBernhard M W Schmidt
Mar 9, 2017·International Journal of Molecular Sciences·Scott M MacKenzieEleanor Davies
Jul 15, 2016·International Journal of Molecular Sciences·Moritz BinderManish Kohli
Sep 17, 2017·Physiological Genomics·Peter A Doris
Apr 19, 2018·International Journal of Endocrinology·Afifah Binti Azam, Elena Aisha Binti Azizan
May 31, 2020·Scientific Reports·Redouane AherrahrouZouhair Aherrahrou
Jun 3, 2021·Cells·Axel KünstnerZouhair Aherrahrou
Sep 7, 2021·Frontiers in Genetics·Siphiwe N DlaminiJulia H Goedecke
Sep 19, 2020·Cancer Chemotherapy and Pharmacology·Stefania CrucittaRomano Danesi