INTERLEUKIN 8 PROMOTER POLYMORPHISM PREDICTS THE INITIAL RESPONSE TO BEVACIZUMAB TREATMENT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION

被引:30
|
作者
Hautamaki, Asta [1 ]
Kivioja, Jarno [2 ]
Vavuli, Satu [3 ,4 ,5 ]
Kakko, Sakari [4 ,5 ]
Savolainen, Eeva-Riitta [6 ]
Savolainen, Markku J. [4 ,5 ]
Liinamaa, M. Johanna [3 ,4 ,5 ]
Seitsonen, Sanna [1 ]
Onkamo, Paivi [7 ]
Jarvela, Irma [2 ]
Immonen, Ilkka [1 ]
机构
[1] Univ Helsinki, Cent Hosp, Dept Ophthalmol, Helsinki 00029, Finland
[2] Univ Helsinki, Dept Med Genet, Helsinki 00029, Finland
[3] Univ Oulu, Dept Ophthalmol, Inst Clin Med, SF-90220 Oulu, Finland
[4] Univ Oulu, Dept Internal Med, Clin Res Ctr, SF-90220 Oulu, Finland
[5] Univ Oulu, Bioctr Oulu, Oulu, Finland
[6] Oulu Univ Hosp, Dept Clin Chem, Oulu, Finland
[7] Univ Helsinki, Dept Biosci, Helsinki 00029, Finland
来源
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES | 2013年 / 33卷 / 09期
关键词
bevacizumab; exudative AMD; interleukin; 8; optical coherence tomography; pharmacogenetics; single-nucleotide polymorphism; treatment response; COMPLEMENT-FACTOR-H; RETINAL VEIN OCCLUSION; AORTIC ENDOTHELIAL-CELLS; C-REACTIVE PROTEIN; INTRAVITREAL BEVACIZUMAB; GENE-EXPRESSION; ERYTHROPOIETIN GENE; AQUEOUS-HUMOR; SIGNIFICANT ASSOCIATION; JAPANESE POPULATION;
D O I
10.1097/IAE.0b013e318285cf92
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: To study the association of single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes with the response to bevacizumab treatment in exudative age-related macular degeneration. Methods: Clinical records, smoking history, optical coherence tomography, and angiographies of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra-or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months. Results: Interleukin 8 promoter polymorphism -251A/T was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of -251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted poorer outcome. Visual acuity change was better in responders than in nonresponders (P = 0.006). Baseline lesion size (P = 0.006) and retinal cysts after the treatment (P < 0.001) correlated with less visual acuity gain. Conclusion: The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.
引用
收藏
页码:1815 / 1827
页数:13
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