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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.

SUBMITTER: Giri A

PROVIDER: S-EPMC4497718 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Giri Ayush A Edwards Todd L TL Motley Saundra S SS Byerly Susan H SH Fowke Jay H JH

PloS one 20150709 7

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 ...[more]

PMID: 26158673

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Project description:BackgroundBenign prostatic enlargement (BPE) causes discomfort in daily life, including lower urinary tract symptoms (LUTSs) caused by the enlarged prostate, and requires long-term management as a chronic, irreversible disease. To improve LUTS, certain complementary therapies have been used with or without doctors' directions. Conventional treatments and complementary therapies tend to be combined unsystematically, depending on patient preference; thus, research for safe and efficient combination therapy is warranted.MethodsTwenty-nine participants were randomly assigned to an integrative group (IG, n = 15) or a conventional group (CG, n = 14). The IG received moxibustion (twice weekly for 4 weeks, at the acupuncture points SP6, LR3, and CV4) and conventional medication for 4 weeks, followed by conventional medication alone for 8 weeks. The CG received conventional medication alone for 12 weeks. The outcome measures were International Prostate Symptom Score (IPSS), patient's global impression of changes (PGIC), maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), and frequency-volume chart.ResultsTotal IPSS (IG, -2.4 ± 4.2; CG, 0.9 ± 4.0; P = .039), PGIC-A (IG, 3.5 ± 1.0; CG, 2.2 ± 1.0; P = .001), and PGIC-B (IG, 3.5 ± 0.1; CG, 4.7 ± 0.6; P = .004) were significantly improved in the IG compared with the CG, 4 weeks after baseline. Among the IPSS items, incomplete emptying (IG, -0.6 ± 0.7; CG, 0.4 ± 1.2; P = .019), straining (IG, -0.6 ± 0.8; CG, 0.2 ± 1.2; P = .046), and nocturia (IG, -0.8 ± 1.4; CG, 0.1 ± 1.0; P = .045) showed significant differences. The Qmax and PVR volume did not differ significantly at 12 weeks after the baseline.ConclusionMoxibustion can be considered an adjunct therapy to improve LUTS in BPE patients. A full-sized randomized controlled trial would be feasible with comparator modifications and an extended study period. The study design should include a placebo group and narrow the eligibility to subjects who do not respond well to conventional treatments.

Dataset Information

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

Publications

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

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