Genetic determinants of metabolism and benign prostate enlargement

Associations with prostate volume

Ayush Giri, Todd L. Edwards, Saundra S. Motley, Susan H. Byerly, Jay Fowke

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0132028
JournalPloS one
Volume10
Issue number7
DOIs
StatePublished - Jul 9 2015

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Polymorphism
Metabolism
single nucleotide polymorphism
Prostate
Single Nucleotide Polymorphism
Nucleotides
metabolism
Biopsy
prostatic neoplasms
Prostatic Hyperplasia
hyperplasia
biopsy
obesity
Linear Models
Prostatic Neoplasms
Obesity
loci
Genetic Loci
metabolic diseases
meta-analysis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Genetic determinants of metabolism and benign prostate enlargement : Associations with prostate volume. / Giri, Ayush; Edwards, Todd L.; Motley, Saundra S.; Byerly, Susan H.; Fowke, Jay.

In: PloS one, Vol. 10, No. 7, e0132028, 09.07.2015.

Research output: Contribution to journalArticle

Giri, Ayush ; Edwards, Todd L. ; Motley, Saundra S. ; Byerly, Susan H. ; Fowke, Jay. / Genetic determinants of metabolism and benign prostate enlargement : Associations with prostate volume. In: PloS one. 2015 ; Vol. 10, No. 7.
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