Dataset Information

The genetic variant rs4073 A?T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration.

ABSTRACT: PURPOSE:To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking. METHODS:Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A?T, CFH rs1061170 T?C, ARMS2 rs10490924 G?T and C3 rs2230199 C?G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed. RESULTS:Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD. CONCLUSION:Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD.

SUBMITTER: Hautamaki A

PROVIDER: S-EPMC4758390 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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The genetic variant rs4073 A→T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration.

Hautamäki Asta A Seitsonen Sanna S Holopainen Juha M JM Moilanen Jukka A JA Kivioja Jarno J Onkamo Päivi P Järvelä Irma I Immonen Ilkka I

Acta ophthalmologica 20150708 8

<h4>Purpose</h4>To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking.<h4>Methods</h4>Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospecti ...[more]

PMID: 26154559

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Project description:Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and a useful platform for developing new therapies.

Dataset Information

The genetic variant rs4073 A?T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration.

Publications

The genetic variant rs4073 A→T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration.

Similar Datasets

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