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

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 diso...

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Autores principales: Giri, Ayush, Edwards, Todd L., Motley, Saundra S., Byerly, Susan H., Fowke, Jay H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497718/
https://www.ncbi.nlm.nih.gov/pubmed/26158673
http://dx.doi.org/10.1371/journal.pone.0132028
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author Giri, Ayush
Edwards, Todd L.
Motley, Saundra S.
Byerly, Susan H.
Fowke, Jay H.
author_facet Giri, Ayush
Edwards, Todd L.
Motley, Saundra S.
Byerly, Susan H.
Fowke, Jay H.
author_sort Giri, Ayush
collection PubMed
description 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.
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spelling pubmed-44977182015-07-14 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 H. PLoS One Research Article 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. Public Library of Science 2015-07-09 /pmc/articles/PMC4497718/ /pubmed/26158673 http://dx.doi.org/10.1371/journal.pone.0132028 Text en © 2015 Giri et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Giri, Ayush
Edwards, Todd L.
Motley, Saundra S.
Byerly, Susan H.
Fowke, Jay H.
Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume
title Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume
title_full Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume
title_fullStr Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume
title_full_unstemmed Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume
title_short Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume
title_sort genetic determinants of metabolism and benign prostate enlargement: associations with prostate volume
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497718/
https://www.ncbi.nlm.nih.gov/pubmed/26158673
http://dx.doi.org/10.1371/journal.pone.0132028
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