A case-based evaluation of SRD5A1, SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH.
In men with a clinical diagnosis of benign prostatic hyperplasia (BPH), polytomous logistic regression analysis was conducted to evaluate associations between two silent polymorphisms in SRD5A1 (codon positions 30 and 116), two polymorphisms in SRD5A2 (Val89Leu substitution and C to T transition in intron 1), a trinucleotide (CAG)n repeat in androgen receptor (AR), and an Arg492Cys substitution in ADRA1A and clinical parameters that characterize severity of BPH. Candidate gene selection was based on two mechanistic pathways targeted by pharmacotherapy for BPH: (1) androgen metabolic loci contributing to prostate growth (static obstruction); and (2) factors affecting smooth muscle tone (dynamic obstruction). Polymorphisms in SRD5A2 were not associated with severity of BPH; however, SRD5A1 polymorphisms were associated with severity of BPH. The process(es) in which these silent single-nucleotide polymorphisms (SNPs) influence BPH phenotypes is unknown and additional studies will be needed to assess whether these SNPs have direct functional consequences. The characterization of additional molecular factors that contribute to static and dynamic obstruction may help predict response to pharmacotherapy and serve to identify novel drug targets for the clinical management of BPH.
Klotsman
M
M
Department of Epidemiology, University of North Carolina School of Public Health, Chapel Hill, NC, USA. michael.x.klotsman@gsk.com
Weinberg
C R
CR
Davis
K
K
Binnie
C G
CG
Hartmann
K E
KE
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000368:Aged; D003062:Codon / Q000235:genetics; D006801:Humans; D008297:Male; D009129:Muscle Tonus / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011467:Prostate / Q000033:anatomy & histology; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D018911:Trinucleotide Repeats
D003062:Codon; D011944:Receptors, Androgen; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C476566:steroid-5alpha-reductase type 1