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健康墨西哥受试者中β1肾上腺素能受体(ADRB1)和β2肾上腺素能受体(ADBR2)基因多态性与局部用倍他洛尔的降眼压反应

ADRB1 and ADBR2 gene polymorphisms and the ocular hypotensive response to topical betaxolol in healthy Mexican subjects.

作者信息

Messina Baas Olga, Pacheco Cuellar Guillermo, Toral-López Jaime, Lara Huerta Silvia Fanny, Gonzalez-Huerta Luz María, Urueta-Cuellar Héctor, Rivera-Vega Ma Refugio, Babayan-Mena Ignacio, Cuevas-Covarrubias Sergio A

机构信息

Department of Ophtalmology .

出版信息

Curr Eye Res. 2014 Nov;39(11):1076-80. doi: 10.3109/02713683.2014.900807. Epub 2014 Apr 21.

DOI:10.3109/02713683.2014.900807
PMID:24749907
Abstract

BACKGROUND

The β adrenergic receptors (ADRB) are expressed in the ciliary body and trabecular meshwork, structures involved in aqueous humor production and outflow, respectively. ADRB are members of the adrenergic family of G-protein-coupled receptors. Topic β blockers have a good local and systemic tolerance; they reduce the aqueous humor production and eye strain blocking the ADRB of the ciliary body and interfering with adenylate cyclase. However, the ocular hypotensive response is not the same in all patients and could be mediated by the polymorphisms of the ADRB genes.

MATERIALS AND METHODS

Seventy-two healthy subjects were studied after treatment with topical betaxolol in both eyes. We analyzed ADRB1 and ADRB2 gene polymorphisms by PCR and automated DNA sequencing.

RESULTS

There was statistically significant difference between baseline intraocular pressure (IOP) and final IOP of both eyes (baseline IOP 16.2 ± 1.2 - follow-up IOP 13.6 ± 2.0 (mean difference-2.5 ± 1.3, p < 0.001). Gly389 had a higher baseline IOP than Arg389 (17.0 ± 1.2 mmHg versus 16.0 ± 1.2 mmHg; p = 0.02), and conversely Arg389 had a greater magnitude of response than Gly389 to betaxolol therapy (-2.9 ± 1.1 mmHg versus -0.7 ± 0.4 mmHg; p < 0.001). Gln27 had a higher response than Glu27 (-2.7 ± 1.3 mmHg versus -1.9 ± 1.0; p = 0.02).

CONCLUSION

Arg389 polymorphism of the ADRB1 gene and Gln27 polymorphism of the ADRB2 gene were associated with the hypotensive response to topic betaxolol in healthy Mexican volunteers.

摘要

背景

β肾上腺素能受体(ADRB)在睫状体和小梁网中表达,这两个结构分别参与房水生成和流出。ADRB是G蛋白偶联受体肾上腺素能家族的成员。局部用β受体阻滞剂具有良好的局部和全身耐受性;它们通过阻断睫状体的ADRB并干扰腺苷酸环化酶来减少房水生成和眼内压。然而,并非所有患者的眼压降低反应都相同,可能由ADRB基因的多态性介导。

材料和方法

对72名健康受试者双眼局部使用倍他洛尔治疗后进行研究。我们通过聚合酶链反应(PCR)和自动DNA测序分析ADRB1和ADRB2基因多态性。

结果

双眼的基线眼压(IOP)与最终眼压之间存在统计学显著差异(基线眼压16.2±1.2 - 随访眼压13.6±2.0(平均差异 - 2.5±1.3,p < 0.001)。甘氨酸389(Gly389)的基线眼压高于精氨酸389(Arg389)(17.0±1.2mmHg对16.0±1.2mmHg;p = 0.02),相反,精氨酸389对倍他洛尔治疗的反应幅度大于甘氨酸389(-2.9±1.1mmHg对 - 0.7±0.4mmHg;p < 0.001)。谷氨酰胺27(Gln27)的反应高于谷氨酸27(Glu27)(-2.7±1.3mmHg对 - 1.9±1.0;p = 0.02)。

结论

在健康的墨西哥志愿者中,ADRB1基因的精氨酸389多态性和ADRB2基因的谷氨酰胺27多态性与局部使用倍他洛尔的降压反应相关。

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