终生早泄的外周通路基因变异:中国汉族男性CYP19A1、CYP1A1和CYP1A2酶的多态性。

IF 2.6 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Sexual Medicine Pub Date : 2024-09-19 eCollection Date: 2024-08-01 DOI:10.1093/sexmed/qfae056
Fei Wang, Defan Luo, Jianxiang Chen, Cuiqing Pan, Zhongyao Wang, Housheng Fu, Jiangbing Xu, Meng Yang, Cun Zhou, Rui Li, Shaowei Mo, Liying Zhuang, Weifu Wang
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引用次数: 0

摘要

背景:最近开展的遗传关联研究侧重于中心通路,以调查易感等位基因与终身早泄(LPE)风险之间的相关性。然而,与外周通路相关的基因仍然缺乏记录:在这项研究中,我们旨在调查与外周基因 CYP19A1、CYP1A1 和 CYP1A2 相关的单核苷酸多态性(SNPs)与 LPE 风险之间的关系:从 2017 年 8 月至 2020 年 8 月,共招募了 511 名参与者(139 名 LPE 患者和 372 名对照者)。经过培训的专业医务人员根据国际性医学会制定的标准定义对 LPE 进行诊断。研究人员选择了 9 个候选 SNPs,并使用 MassARRAY 系统进行了基因分型。使用 χ2 检验比较了患者和对照组中 SNPs 的等位基因和基因型频率。使用 PLINK 1.9 版进行逻辑回归分析,并对年龄进行调整,以计算几率比(ORs)和 95% 置信区间(CIs)。Haploview 软件用于分析连锁不平衡和单倍型分布。使用多因素降维法评估了候选 SNPs 之间关于 LPE 风险的相互作用。利用方差分析评估了所选多态性与特定特征之间的关系:位于 CYP19A1(rs4646、rs17601876)、CYP1A1(rs1048943)和 CYP1A2(rs762551、rs2470890)基因中的杂合 SNP 与 LPE 风险有显著相关性:本研究结果证实,CYP19A1(rs4646 AC vs CC:OR,1.84;CI,1.10-3.09;rs17601876 AG vs GG:OR,1.80;CI,1.06-3.05)和 CYP1A1 基因(rs1048943 CT vs TT:OR,1.71;CI,1.02-2.87)中的杂合 SNPs 可显著增加 LPE 风险。不同基因型的 CYP1A1-rs1048943 参与者在早泄诊断工具(P =.002)和国际勃起功能指数-5(International Index of Erectile Function-5,P =.020)方面的得分有明显差异。单倍型分析表明,CYP1A2_rs762551-rs2470890(D' = 1.00)具有很强的连锁不平衡:本研究及其他关于 LPE 遗传决定因素和潜在致病机制的研究结果可为 LPE 患者的诊断和治疗提供更多机会:在这项关于CYP基因变异男性LPE的研究中,我们填补了目前的研究空白。然而,病例组和对照组中有关吸烟和饮酒等风险因素的数据并不完整。在今后的研究中,我们将扩大样本量,增加有关风险因素的数据,以进行更精确的评估:总之,外周基因 CYP19A1、CYP1A1 和 CYP1A2 的多态性可能是导致中国汉族男性 LPE 的原因之一。
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Peripheral pathway gene variants in lifelong premature ejaculation: CYP19A1, CYP1A1, and CYP1A2 enzymes polymorphisms in Chinese Han men.

Background: Recent genetic association studies focusing on central pathways have been performed to investigate the correlation between susceptibility alleles and the risk of lifelong premature ejaculation (LPE). However, there remains a dearth of documented genes associated with peripheral pathways.

Objective: In this study we aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) associated with the peripheral genes CYP19A1, CYP1A1, and CYP1A2 and the risk of LPE.

Methods: From August 2017 to August 2020, a total of 511 participants (139 LPE patients and 372 controls) were recruited. Trained medical professionals diagnosed LPE according to the standard definition set by the International Society for Sexual Medicine. Nine candidate SNPs were chosen and genotyped using the MassARRAY system. Allele and genotype frequencies of the SNPs among patients and controls were compared using the χ2 test. Logistic regression analysis, adjusted for age, was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using PLINK version 1.9. Haploview software was employed to analyze linkage disequilibrium and haplotype distribution. The interaction among candidate SNPs concerning LPE risk was evaluated using multifactor dimensionality reduction. The relationship between selected polymorphisms and specific features was assessed using analysis of variance.

Outcome: Heterozygous SNPs located in the CYP19A1 (rs4646, rs17601876), CYP1A1 (rs1048943), and CYP1A2 (rs762551, rs2470890) genes showed significant correlations with the risk of LPE.

Results: The findings of this study confirmed that heterozygous SNPs in the CYP19A1 (rs4646 AC vs CC: OR, 1.84; CI, 1.10-3.09; rs17601876 AG vs GG: OR, 1.80; CI, 1.06-3.05) and CYP1A1 genes (rs1048943 CT vs TT: OR, 1.71; CI, 1.02-2.87), respectively, can significantly increase the LPE risk. Participant scores for the Premature Ejaculation Diagnostic Tool (P =.002) and International Index of Erectile Function-5 (P =.020) differed significantly by genotype for the different genotypes of CYP1A1-rs1048943. Haplotype analysis revealed strong linkage disequilibrium under CYP1A2_rs762551-rs2470890 (D' = 1.00).

Clinical implications: The findings of this and other investigations of genetic determinants and potential pathogenic mechanisms of LPE may advance diagnostic and therapeutic opportunities in LPE patients.

Strengths and limitations: In this study of LPE in men with CYP gene variants we addressed a current research gap. However, data on risk factors such as smoking and drinking were incomplete in both the case and control groups. In future studies we will expand the sample size and enhance data on risk factors for more precise assessments.

Conclusion: In summary, polymorphisms in the peripheral genes CYP19A1, CYP1A1, and CYP1A2 may play a role in LPE among Chinese men of the Han population.

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来源期刊
Sexual Medicine
Sexual Medicine MEDICINE, GENERAL & INTERNAL-
CiteScore
5.40
自引率
0.00%
发文量
103
审稿时长
22 weeks
期刊介绍: Sexual Medicine is an official publication of the International Society for Sexual Medicine, and serves the field as the peer-reviewed, open access journal for rapid dissemination of multidisciplinary clinical and basic research in all areas of global sexual medicine, and particularly acts as a venue for topics of regional or sub-specialty interest. The journal is focused on issues in clinical medicine and epidemiology but also publishes basic science papers with particular relevance to specific populations. Sexual Medicine offers clinicians and researchers a rapid route to publication and the opportunity to publish in a broadly distributed and highly visible global forum. The journal publishes high quality articles from all over the world and actively seeks submissions from countries with expanding sexual medicine communities. Sexual Medicine relies on the same expert panel of editors and reviewers as The Journal of Sexual Medicine and Sexual Medicine Reviews.
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