Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume.

Giri A, Edwards TL, Motley SS, Byerly SH, Fowke JH
PLoS One. 2015 10 (7): e0132028

PMID: 26158673 · PMCID: PMC4497718 · DOI:10.1371/journal.pone.0132028

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.

MeSH Terms (20)

Adult Aged Collagen Type IV Genetic Loci Genotype Humans Linear Models Male Middle Aged Nerve Tissue Proteins Obesity Organ Size Polymorphism, Single Nucleotide Prostate Prostatic Hyperplasia Prostatic Neoplasms Ribosomal Proteins Sodium Channels Symporters Ultrasonography

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