前列腺素F2α类降眼压药物引发心血管副作用的临床病例及其遗传相关性  

Glaucoma cases with prostaglandin F2αanalogs associated cardiovascular side effects and its possible genetic mechanisms

作　　者：李晓红 平美萱 王希振 王可 张达人 何芬 刘果 刘旭阳 Li Xiaohong;Ping Meixuan;Wang Xizhen;Wang Ke;Zhang Daren;He Fen;Liu Guo;Liu Xuyang(Department of Biopharmaceutics, West China School of Pharmacy, Sichuan University, Chengdu 610041, China;Shenzhen Eye Hospital, Jinan University, Shenzhen 518020, China;Xiamen Eye Center, Xiamen University, Xiamen 361001, China;Department of Ophthalmology, Shenzhen People's Hospital, Shenzhen 518020, China)

机构地区：[1]四川大学华西药学院生物技术药物学系,成都610041 [2]暨南大学深圳眼科医院 [3]厦门大学厦门眼科中心 [4]深圳市人民医院眼科

出　　处：《临床眼科杂志》2021年第1期14-19,共6页Journal of Clinical Ophthalmology

基　　金：四川省卫生和计划生育委员会科研课题(16PJ226);国家自然科学基金面上项目(81770924)。

摘　　要：目的报道前列腺素(PG)F2α类降眼压药物引发心血管副作用的临床病例,并初探其遗传背景。方法收集临床上使用PGF2α类药物出现心血管副作用的原发性开角型青光眼病例,进行候选基因分析。结果我们发现了3例滴用PGF2α类药物后出现心血管副作用的病例,其中2例滴用拉坦前列腺素后出现症状,1例滴用贝美前列腺素后出现症状。拉坦前列腺素引发副作用的病例PGF2α受体(FP)基因型变异(rs3753380 TT,rs3766355 CC),斯钙素1(STC1)基因5’-非翻译区基因型变异(rs1438452 TC,rs1438453 AC)。结论患者在使用PGF2α类药物后可能产生心血管副作用,其机制可能与患者的降眼压机制相关蛋白,如受体FP及其下游效应蛋白STC1的基因变异有关。Objective To report cases with prostaglandin F2α(PGF2α)analogs associated cardiovascular side effects and investigate the possible genetic mechanisms.Methods Three patients with primary open angle glaucoma,who developed significant cardiovascular effects after topical application of PGF2αanalogs,were enrolled in this study.Results Patients with cardiovascular effects induced by latanoprost had genotype variation(rs3753380 TT and rs3766355 CC)leading to decreased expression of prostaglandin F receptor(FP),and genotype variation(rs1438452 TC and rs1438453 AC)in the 5’-untranslated region of stanniocalcin 1(STC1)gene,which leads to microsatellite DNA instability.Conclusions The cardiovascular side effects of topical PGF2αanalogs might be attributed to the gene mutation of some proteins,which are involved in the intraocular pressure-lowering mechanism of PGF2αanalogs,such as FP and STC1.

关 键 词：青光眼 前列腺素F2α类药物 心血管系统 前列腺素F受体 斯钙素1 

分 类 号：R54[医药卫生—心血管疾病]