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ADRB3:rs4994 与女性膀胱过度活动症单次膀胱内注射肉毒毒素后 6 个月尿动力学结果的关联分析。

Association analysis of ADRB3:rs4994 with urodynamic outcome, six months after a single intra-detrusor injection of botulinum toxin, in women with overactive bladder.

机构信息

Department of Gynecology, Endocrinology and Gynecological Oncology, Pomeranian Medical University, Szczecin, Poland.

Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland.

出版信息

Pharmacol Rep. 2024 Dec;76(6):1489-1500. doi: 10.1007/s43440-024-00647-9. Epub 2024 Sep 11.

Abstract

BACKGROUND

Intra-detrusor injection of botulinum neurotoxin type A (BoNT/A) is recommended as a possible treatment for patients with overactive bladder (OAB) in whom first-line therapies have failed. The c.190T > C (rs4994) polymorphism in the gene encoding the beta-3 adrenergic receptor (ADRB3) has been suggested to be associated with predisposition to OAB or with response to OAB treatment via a cholinergic muscarinic receptor antagonist. This prospective study aimed to use a urodynamic parameter-based assessment of response, six months after a single intra-detrusor injection of BoNT/A in female OAB patients, to elucidate possible association with the ADRB3 polymorphism.

METHODS

The study group consisted of 138 consecutive, Polish, adult, female OAB patients. Urodynamic parameters were recorded before injection of BoNT/A and at six months after administration. ADRB3:rs4994 variants were identified by the sequencing of genomic DNA extracted from buccal swabs.

RESULTS

Apart from baseline, and relative, increase in Maximum Cystometric Capacity (MCC) six months after BoNT/A injection, no significant differences were found in urodynamic parameters between reference TT homozygotes and women with at least one C allele.

CONCLUSIONS

Our results do not exclude that ADRB3:rs4994 variants are associated with a positive urodynamic test-based response to intra-detrusor injection of BoNT/A in females with OAB.

摘要

背景

对于一线治疗失败的膀胱过度活动症(OAB)患者,推荐经尿道内注射肉毒杆菌毒素 A(BoNT/A)作为一种可能的治疗方法。编码β-3 肾上腺素能受体(ADRB3)的基因中的 c.190T > C(rs4994)多态性被认为与 OAB 的易感性或通过胆碱能毒蕈碱受体拮抗剂对 OAB 治疗的反应有关。本前瞻性研究旨在使用单一经尿道内注射 BoNT/A 治疗后 6 个月的尿动力学参数评估反应,以阐明与 ADRB3 多态性的可能关联。

方法

研究组包括 138 名连续的波兰成年女性 OAB 患者。在注射 BoNT/A 前和给药后 6 个月记录尿动力学参数。通过从口腔拭子中提取的基因组 DNA 测序确定 ADRB3:rs4994 变体。

结果

除了注射 BoNT/A 后 6 个月最大膀胱容量(MCC)的基线和相对增加外,参考 TT 纯合子和至少有一个 C 等位基因的女性之间的尿动力学参数没有发现显著差异。

结论

我们的结果不排除 ADRB3:rs4994 变体与女性 OAB 经尿道内注射 BoNT/A 后基于尿动力学检查的阳性反应有关。

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