Abstract：
BACKGROUND: Cardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood.
OBJECTIVE: Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high-risk cardiovascular disease patients.
METHODS: Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T-786C), genotyped by fluorescence polarization assays, were registered. The 27-bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Association analyses were run with the R-3.2.0 software.
RESULTS: A significant association between endothelial nitric oxide synthase 786-TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 ± 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3-months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 ± 16 scores, the International Index of Erectile Function-Erectile Function 21 ± 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 ± 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894-T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction.
CONCLUSIONS: Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high-risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.
OBJECTIVE: Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high-risk cardiovascular disease patients.
METHODS: Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T-786C), genotyped by fluorescence polarization assays, were registered. The 27-bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Association analyses were run with the R-3.2.0 software.
RESULTS: A significant association between endothelial nitric oxide synthase 786-TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 ± 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3-months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 ± 16 scores, the International Index of Erectile Function-Erectile Function 21 ± 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 ± 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894-T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction.
CONCLUSIONS: Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high-risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.
摘要：
背景：心血管疾病诱导由内皮型一氧化氮合酶调节的勃起功能障碍和限制阴茎血管充血的射血分数受损。然而,调节内皮功能障碍的机制尚不清楚。
目的：探讨内皮型一氧化氮合酶基因多态性对高危心血管疾病患者勃起功能障碍和药物治疗优化的功能影响。
方法：纳入有勃起功能障碍症状的患者和接受男科治疗的患者（n=112）。临床数据和内皮型一氧化氮合酶rs1799983（G894T）和rs2070744（T-786C），通过荧光偏振测定进行基因分型，已注册。通过聚合酶链反应-限制性片段长度多态性分析了内含子4（内含子4b/a）中串联重复多态性的27bp可变数量。用R-3.2.0软件进行关联分析。
结果：在心血管疾病患者（60±9岁，66%严重勃起功能障碍,56%的射血分数)。5型磷酸二酯酶抑制剂3个月后，勃起功能障碍(国际勃起功能指数，50±16分,国际勃起功能指数-勃起功能21±10分，p<0.001）和性生活质量（改良的性生活质量问卷55±23分，p<0.001)有显著改善。心血管射血分数对性生活质量有积极影响(0.1941),在内皮型一氧化氮合酶G894-T等位基因（p=0.076）携带者中，这可能值得未来的分析。62%的病例以勃起功能障碍为主要临床表现，与心血管疾病同时发生。只有前吸烟者和肥胖受试者在心血管疾病之前才出现勃起功能障碍。
结论：我们的研究提供了有关内皮型一氧化氮合酶基因多态性的功能相互作用的全面见解，勃起功能，高危心血管疾病患者的射血分数。未来的治疗策略可以通过包括生活方式改变和表观遗传调节来靶向内皮一氧化氮合酶活性。
目的：探讨内皮型一氧化氮合酶基因多态性对高危心血管疾病患者勃起功能障碍和药物治疗优化的功能影响。
方法：纳入有勃起功能障碍症状的患者和接受男科治疗的患者（n=112）。临床数据和内皮型一氧化氮合酶rs1799983（G894T）和rs2070744（T-786C），通过荧光偏振测定进行基因分型，已注册。通过聚合酶链反应-限制性片段长度多态性分析了内含子4（内含子4b/a）中串联重复多态性的27bp可变数量。用R-3.2.0软件进行关联分析。
结果：在心血管疾病患者（60±9岁，66%严重勃起功能障碍,56%的射血分数)。5型磷酸二酯酶抑制剂3个月后，勃起功能障碍(国际勃起功能指数，50±16分,国际勃起功能指数-勃起功能21±10分，p<0.001）和性生活质量（改良的性生活质量问卷55±23分，p<0.001)有显著改善。心血管射血分数对性生活质量有积极影响(0.1941),在内皮型一氧化氮合酶G894-T等位基因（p=0.076）携带者中，这可能值得未来的分析。62%的病例以勃起功能障碍为主要临床表现，与心血管疾病同时发生。只有前吸烟者和肥胖受试者在心血管疾病之前才出现勃起功能障碍。
结论：我们的研究提供了有关内皮型一氧化氮合酶基因多态性的功能相互作用的全面见解，勃起功能，高危心血管疾病患者的射血分数。未来的治疗策略可以通过包括生活方式改变和表观遗传调节来靶向内皮一氧化氮合酶活性。
