title: Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample.
abstract: OBJECTIVE
  The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters.
  
  
  METHODS
  A random sample of the population-based Herne lower urinary tract symptoms cohort was analysed. All these men underwent a detailed urological work-up. Two polymorphisms in the CYP19A1 gene [rs700518 in exon 4 (A57G); rs10046 at the 3'UTR(C268T)] and one in the 3'UTR of CYP3A4 [rs2740574 (A392G)] were determined by TaqMan assay from genomic DNA of peripheral blood. These polymorphisms were correlated to clinical and laboratory BPH-parameters.
  
  
  RESULTS
  A total of 392 men (65.4 ± 7.0 years; 52-79 years) were analysed. Mean International Prostate Symptom Score (IPSS; 7.5), Q (max) (15.4 ml/s), prostate volume (31 ml) and prostate specific antigen (PSA) (1.8 ng/ml) indicated a typical elderly population. Both polymorphisms in the CYP19A1 gene were not correlated to age, IPSS, Q (max), prostate volume and post-void residual volume. Serum PSA was higher in men carrying the heterozygous rs10046 genotype (2.0 ± 0.1 ng/ml) than in those with the CC-genotype (1.7 ± 0.2 ng/ml, P = 0.012). Men carrying one a mutated allele of the CYP3A4 gene had smaller prostates (27.0 ± 2.0 vs. 32 ± 0.8 ml, P = 0.02) and lower PSA levels (1.6 ± 0.3 vs. 1.9 ± 0.1 ng/ml).
  
  
  CONCLUSIONS
  The inconsistent associations observed herein and for other gene polymorphisms warrant further studies. In general, the data regarding the association of gene polymorphism to BPH-parameters suggest that this disease is caused by multiple rather than a single genetic variant. A rigorous patient selection based on anatomo-pathological and hormonal profile may possible reduce the number of confounders for future studies thus enabling a more detailed assessment of the association between genetic factors and BPH-parameters.
authors.affiliation: Pan-Klinik, Cologne, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Berges
authors.forename: Andrea
authors.initials: A
authors.lastname: Gsur
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Feik
authors.forename: Klaus
authors.initials: K
authors.lastname: Höfner
authors.forename: Theodor
authors.initials: T
authors.lastname: Senge
authors.forename: Ludger
authors.initials: L
authors.lastname: Pientka
authors.forename: Andreas
authors.initials: A
authors.lastname: Baierl
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
authors.forename: Anton
authors.initials: A
authors.lastname: Ponholzer
authors.forename: Stephan
authors.initials: S
authors.lastname: Madersbacher
mesh_terms: D000368:Aged; D000483:Alleles; D001141:Aromatase / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011470:Prostatic Hyperplasia / Q000235:genetics*; D053448:Prostatism / Q000503:physiopathology*; D012044:Regression Analysis; D013739:Testosterone / Q000378:metabolism; D014555:Urination Disorders / Q000235:genetics*
chemical_list: D013739:Testosterone; D001141:Aromatase; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017430:Prostate-Specific Antigen