Gerzenstein Sabrina M, Pletcher Mathew T, Cervino Alessandra C L, Tsinoremas Nicholas F, Young Brandon, Puliafito Carmen A, Fini M Elizabeth, Schwartz Stephen G
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
Ophthalmic Genet. 2008 Dec;29(4):166-70. doi: 10.1080/13816810802320217.
Elevation of intraocular pressure (IOP) following injection of intravitreal triamcinolone acetonide (IVTA) is an important clinical problem. The etiology of the steroid response is poorly understood, although a genetic determinant has long been suspected. We performed a pharmacogenomic association study with glucocorticoid receptor polymorphisms.
Fifty-two patients (56 eyes) who underwent treatment with IVTA for various retinal diseases were genotyped for six well-studied glucocorticoid receptor polymorphisms (ER22/23EK, N363S, BclI, N766N, and single nucleotide polymorphisms (SNPs) within introns 3 and 4).
Three polymorphisms (ER22/23EK, N363S, and the intron 3 SNP) were essentially nonpolymorphic within this population sample and excluded from further analysis. The remaining three polymorphisms (BclI, N766N, and within intron 4) passed the Hardy-Weinberg Equilibrium test, indicating good genotyping quality and normal population distribution of allelic frequency. No statistically significant correlations were found between these three polymorphisms and magnitude of IOP elevation following IVTA, using single point association and haplotype analyses.
In this small, pilot study, we found no statistically significant relationship between glucocorticoid receptor polymorphisms and IOP elevation following IVTA. The precise etiology of the steroid response remains obscure. To our knowledge, this is the first published pharmacogenomic study of this common clinical entity.
玻璃体内注射曲安奈德（IVTA）后眼压（IOP）升高是一个重要的临床问题。尽管长期以来怀疑存在遗传决定因素，但对类固醇反应的病因了解甚少。我们进行了一项关于糖皮质激素受体多态性的药物基因组关联研究。
对52例（56只眼）因各种视网膜疾病接受IVTA治疗的患者进行基因分型，检测6个已充分研究的糖皮质激素受体多态性（ER22/23EK、N363S、BclI、N766N以及内含子3和4内的单核苷酸多态性（SNP））。
在该人群样本中，3种多态性（ER22/23EK、N363S和内含子3 SNP）基本无多态性，被排除在进一步分析之外。其余3种多态性（BclI、N766N和内含子4内的多态性）通过了哈迪-温伯格平衡检验，表明基因分型质量良好且等位基因频率在人群中分布正常。使用单点关联和单倍型分析，未发现这3种多态性与IVTA后IOP升高幅度之间存在统计学显著相关性。
在这项小型试点研究中，我们发现糖皮质激素受体多态性与IVTA后IOP升高之间无统计学显著关系。类固醇反应的确切病因仍不清楚。据我们所知，这是首次发表的关于这一常见临床实体的药物基因组学研究。
