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Randomized Controlled Trial
. 2017 Aug;77(11):1213-1220.
doi: 10.1002/pros.23380. Epub 2017 Jun 28.

A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS)

Rong Na  1   2   3 , Brian T Helfand  1   4 , Haitao Chen  5 , Carly A Conran  1 , Susan E Crawford  1 , Simon W Hayward  1 , Teuvo L J Tammela  6 , Judy Hoffman-Bolton  7 , Siqun L Zheng  1 , Patrick C Walsh  8 , Johanna Schleutker  9 , Elizabeth A Platz  7 , William B Isaacs  8   10 , Jianfeng Xu  1   2
Affiliations
Randomized Controlled Trial

A genetic variant near GATA3 implicated in inherited susceptibility and etiology of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS)

Rong Na et al. Prostate. 2017 Aug.

Abstract

Background: Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common conditions. Little is known about their etiologies except that studies have suggested a substantial heritable component. Our objective is to provide a comprehensive, genome-wide evaluation of inherited risks and possible mechanisms of etiology in BPH.

Methods: We performed a three-stage, genome-wide association study (GWAS) of men from three independent populations, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, the CLUE II cohort, and a Finnish hospital-based population. DNA samples were genotyped using the Illumina HumanOmniExpress BeadChip in REDUCE and CLUE II, and using the Sequenom iPLEX system for the confirmation stage in the Finnish population. A logistic regression model was used to evaluate the association between each SNP and BPH/LUTS.

Results: Fourteen SNPs reached P < 5.0 × 10-4 in the meta-analysis of the two GWASs (CLUE II and REDUCE). A total of 773 SNPs were chosen for the confirmation step in the Finish cohort. Only one SNP (rs17144046) located ∼489 kb downstream of GATA3 remained significant after correction for multiple testing (P < 6.5 × 10-5 ). This SNP marginally reached the GWAS significance level after performing a meta-analysis of the three stages (P-meta = 8.89 × 10-7 ). Expression quantitative trait loci (eQTL) analyses showed that the risk allele (G) of rs17144046 was significantly associated with increased expression of GATA3 (P = 0.017). Reported studies indicated a close correlation between GATA3 and BPH pathogenesis and progression.

Conclusions: Rs17144046 located near GATA3 was significantly associated with BPH/LUTS in three independent populations, but did not reach a stringent GWAS significance level. Genetic variants of GATA3 may play a role in the inherited susceptibility and etiology of BPH/LUTS. Further research in this area is needed.

Keywords: BPH; LUTS; genome-wide association study.

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Conflict of interest statement

Conflict of interest and Disclosure Statement

No known conflict of interest is related to the study

Figures

Figure 1
Figure 1
Manhattan plot: the −log10P-values by chromosome location for BPH/LUTS-associated SNPs in (a) REDUCE trial, (b) CLUE II and (c) meta-analysis of CLUE II and REDUCE
Figure 2
Figure 2
Forest plot: the results from the meta-analysis of the two GWASs and the confirmation study of these two SNPs
Figure 3
Figure 3
Regional plot (LocusZoom plot) of rs17144046
See this image and copyright information in PMC

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