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Original article
DOI: 10.1016/j.oftale.2020.02.017
Roles of IL-8 −251A/T and +781C/T polymorphisms, IL-8 level, and the risk of age-related macular degeneration
Roles de polimorfismos de IL-8, -251A/T y +781C/T, nivel de IL-8, y el riesgo de degeneración macular asociada con la edad
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Z.S. Ulhaqa,
Corresponding author
, G.V. Sorayab
a Departamento de Ciencia Bioquímica, Facultad de Medicina y Ciencias de la Salud, Universidad Estatal Islámica Maulana Malik Ibrahim, Batu, Indonesia
b Departamento de Bioquímica, Facultad de Medicina, Universidad Hasanuddin, Macasar, Indonesia
Received 02 January 2020. Accepted 19 February 2020
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Table 1. Characteristics of individual studies for associations between IL-8 polymorphisms and AMD.
Table 2. Meta-analysis for the association between IL-8 polymorphisms and AMD.
Table 3. Summary of the studies for the IL-8 level between AMD patients and control subjects.
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Abstract
Objective

To clarify the association between IL-8 gene polymorphisms, IL-8 level, towards the risk of age-related macular degeneration (AMD).

Methods

Meta-analysis was performed from available studies that investigated IL-8 −251A/T (rs4073) and +781C/T (rs2227306) polymorphisms and IL-8 levels in patients with AMD and controls.

Results

Overall, the pooled result showed a significant association between AMD with allelic (T vs. C; OR 1.53; p = 0.005), dominant (TT + CT vs. CC; OR 1.95; p = 0.017), homozygous (TT vs. CC; OR 2.03; p = 0.039) and heterozygous (CT vs. CC; OR 1.92; p = 0.032) models of rs2227306; while subgroup analysis revealed a significant association between rs2227306 with wet AMD in allelic (T vs. C; OR 1.69; p = 0.016), recessive (TT vs. CT + CC; OR 1.81; p = 0.00007), and homozygous (TT vs. CC; OR 2.64; p = 0.003) models. No significant association was observed between rs4073 with AMD in all inheritance models. In parallel, patients with AMD, particularly wet AMD had an elevated level of IL-8 compared to control.

Conclusion

This meta-analysis suggests that patients with AMD or wet AMD have higher IL-8 levels compared to control, which is also supported by the evidence that carrier T allele of rs2227306 exhibited an increase in the risk of AMD or wet AMD. Thus, IL-8 +781C/T (rs2227306) polymorphism and the level of intraocular IL-8 may be useful as a biomarker for early detection and a therapeutic target of AMD.

Keywords:
Cytokine
Inflammation
IL-8 polymorphisms
IL-8 level
Age-related macular degeneration
Resumen
Objetivo

Aclarar la asociación entre polimorfismos del gen IL-8 y nivel de IL-8 en el riesgo de degeneración macular asociada a la edad (DMAE).

Métodos

Se realizó un metaanálisis a partir de los estudios disponibles que investigaron los polimorfismos de IL-8 −251A/T (rs4073) y +781C/T (rs2227306), y niveles de IL-8, en pacientes con DMAE y controles.

Resultados

En total, el resultado agrupado mostró una asociación significativa entre DMAE con modelos alélicos (T vs. C; OR 1,53; p = 0,005), dominantes (TT + CT vs. CC; OR 1,95; p = 0,017), homocigotos (TT vs. CC; OR 2,03; p = 0,039) y heterocigotos (CT vs. CC; OR 1,92; p = 0,032) de rs2227306; mientras que el análisis de subgrupos reveló una asociación significativa entre rs2227306 con DMAE húmedo en modelos alélicos (T vs. C; OR 1,69; p = 0,016), recesivos (TT vs. CT + CC; OR 1,81; p = 0,00007), y homocigotos (TT vs. CC; OR 2,64; p = 0,003). No se observó asociación significativa entre rs4073 con DMAE en todos los modelos de herencia. Paralelamente, los pacientes con DMAE, particularmente DMAE húmedo, tenían un nivel elevado de IL-8 en comparación con el control.

Conclusión

Este metaanálisis sugiere que los pacientes con DMAE o DMAE húmedo tienen niveles más altos de IL-8 en comparación con controles, lo que también está respaldado por la evidencia de que el alelo T portador de rs2227306 exhibe un aumento en el riesgo de DMAE o DMAE húmedo. Por lo tanto, el polimorfismo IL-8 +781C/T (rs2227306) y el nivel de IL-8 intraocular pueden ser útiles como biomarcadores para la detección temprana y objetivo terapéutico de DMAE.

Palabras clave:
Citocina
Inflamación
Polimorfismos de IL-8
Nivel de IL-8
Degeneración macular asociada con la edad

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