The effect of β3-adrenoceptor gene polymorphisms on lower urinary tract function in males

Haga, Nobuhiro; Okabe, Yuki; Miyazaki, Takeshi; Tsubouchi, Kazuna; Akaihata, Hidenori; Hata, Junya; Honda, Ryumon; Matsuoka, Kanako; Ogawa, Soichiro; Kojima, Yoshiyuki

doi:10.1007/s00345-020-03531-2

Cited by 1 publication

(3 citation statements)

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“…A fifth study genotyped 376 men with localized prostate cancer undergoing robot-assisted prostatectomy in a single center in Japan of which 129 carried the 64Arg alle (114 heterozygous and 15 homozygous) and 247 did not. 11 The authors defined the presence of OAB by taking a muscarinic receptor antagonist or a β 3 -AR agonist and BPH by taking an α 1 -AR antagonist, phosphodiesterase type 5 inhibitor, and/or 5α-reductase inhibitor. By this definition 25% of homozygous 64Trp carriers and 21% of 64Arg carriers had BPH and 1% in each group had OAB and both groups were pooled for analysis.…”

Section: Allele Frequency In Control Versus Disease Populationsmentioning

confidence: 99%

“…Another all‐male study compared LUTS according to genotype in 376 men undergoing robot‐assisted radical prostatectomy in a single center in Japan, of which 129 carried the 64Arg alle (114 heterozygous and 15 homozygous) and 247 did not 11 . The two groups were similar in age, PSA, prostate size, Gleason score, and the prevalence of concomitant hypertension (47% vs. 50%), diabetes (12% vs. 15%), BPH (25% vs. 21%), and OAB (1% each).…”

Section: Association Of Polymorphisms With Disease Severitymentioning

confidence: 99%

“…4,5 The Trp64Arg polymorphism is in linkage with other polymorphisms outside the coding region and forms a haploblock consisting of either the Trp haplotype (190t, 1219g, 2135a, 2502g, 3558a plus a nine repeat thymine guanine (TG) dinucleotide length polymorphism) and the Arg haplotype (190c, 1219t, 2135g, 2502c, 3558t plus an eight repeat TG. 6,7 The frequency of the 64Arg allele in Caucasian populations typically is about 8%, 6,8,9 with slightly different values in other ethnicities including Japanese (19%-25%) [10][11][12] and Pima Indians (31%). 4 Accordingly, homozygous 64Arg carriers are rare (<1% in Caucasians).…”

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confidence: 99%

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Are β₃‐adrenoceptor gene polymorphisms relevant for urology?

Michel

2022

Neurourology and Urodynamics

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Aims: β 3 -adrenoceptors (ARs) are an important drug target for the treatment of overactive bladder syndrome (OAB) and are under investigation for other indications. The human β 3 -AR gene is polymorphic; an exchange of amino acid tryptophan (Trp) for arginine (Arg) in position 64 of the receptor protein is the most frequent and best-studied polymorphism. A narrative review on the impact of β 3 -AR polymorphisms on urological disease and its treatment is presented.Results: Two out of four studies have reported that the 64Arg allele was found more frequently in subjects with OAB than in healthy controls. A large study in a highly selective population (men undergoing prostatectomy for cancer treatment) did not confirm this. On the other hand, studies examining symptom severity typically found little difference between 64Arg and 64Trp carriers. In vitro studies with endogenously expressed β 3 -AR reported a decreased lipolytic response in human adipose tissue. Studies with heterologously expressed receptors sometimes found a decreased responsiveness to agonists including β 3 -AR agonists, but others did not confirm that. Conclusions: The overall evidence points to carriers of the 64Arg genotype expressing fewer and/or hypofunctional β 3 -ARs and being associated with the presence of OAB but such findings were only detected inconsistently. If this hypofunctionality exists, the consequences may be of insufficient magnitude to allow a robust detection. Only adequately powered studies comparing responses with a β 3 -AR agonist in 64Arg carriers versus wild-type patients can address this.

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Section: Allele Frequency In Control Versus Disease Populationsmentioning

confidence: 99%

Section: Association Of Polymorphisms With Disease Severitymentioning

confidence: 99%