Interleukin-8 promoter polymorphism is associated with the initial repose to bevacizumab in AMD treatment

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Abstract

Purpose

To study the association of potential key single-nucleotide polymorphisms with the short-term anatomic response to bevacizumab treatment in exudative age-related macular degeneration (AMD).

Methods

Clinical data 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. Representative single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes were analysed.

Results

Interleukin 8 promoter polymorphism −251A/T,conferring a more acitve interleuking-8 system, 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 a poorer outcome.

Conclusion

The interleukin -8 pathway may modulate the early anatomic response to anti-VEGF treatment in AMD. A possible activation of interleukin -8 production in patients may represent a compensatory mechanism to chronic blockade of VEGF signalling in AMD lesions

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