title: Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume.
abstract: Prostate enlargement leading to clinical benign prostatic hyperplasia (BPH) is associated with metabolic dysregulation and obesity. The genetic basis of this association is unclear. Our objective was to evaluate whether single nucleotide polymorphisms (SNPs) previously associated with metabolic disorders are also associated with prostate volume (PV). Participants included 876 men referred for prostate biopsy and found to be prostate cancer free. PV was measured by transrectal ultrasound. Samples were genotyped using the Illumina Cardio-MetaboChip platform. Multivariable adjusted linear regression models were used to evaluate SNPs (additive coding) in relation to natural-log transformed (log) PV. We compared SNP-PV results from biopsy-negative men to 442 men with low-grade prostate cancer with similar levels of obesity and PV. Beta-coefficients from the discovery and replication samples were then aggregated with fixed effects inverse variance weighted meta-analysis. SNP rs11736129 (near the pseudo-gene LOC100131429) was significantly associated with log-PV (beta: 0.16, p-value 1.16x10(-8)) after adjusting for multiple testing. Other noteworthy SNPs that were nominally associated (p-value < 1x10(-4)) with log-PV included rs9583484 (intronic SNP in COL4A2), rs10146527 (intronic SNP in NRXN3), rs9909466 (SNP near RPL32P31), and rs2241606 (synonymous SNP in SLC12A7). We found several SNPs in metabolic loci associated with PV. Further studies are needed to confirm our results and elucidate the mechanism between these genetic loci, PV, and clinical BPH.
authors.affiliation: Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Ayush
authors.initials: A
authors.lastname: Giri
authors.affiliation: Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, United States of America; Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, United States of America; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Edwards
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Saundra S
authors.initials: SS
authors.lastname: Motley
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Byerly
authors.affiliation: Institute for Medicine and Public Health, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, United States of America; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America; Department of Surgical Urology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Fowke
mesh_terms: D000328:Adult; D000368:Aged; D024141:Collagen Type IV / Q000235:genetics; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009765:Obesity / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011467:Prostate / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011470:Prostatic Hyperplasia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D012269:Ribosomal Proteins / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D027981:Symporters / Q000235:genetics; D014463:Ultrasonography; D000096922:K Cl- Cotransporters
chemical_list: D024141:Collagen Type IV; D009419:Nerve Tissue Proteins; D012269:Ribosomal Proteins; D015222:Sodium Channels; D027981:Symporters; C502625:COL4A2 protein, human; C119651:SLC12A7 protein, human; D000096922:K Cl- Cotransporters; C082354:neurexin IIIalpha; C041806:ribosomal protein L32