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

PurposeTo 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.MethodsMedical 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.ResultsYounger 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.ConclusionOut 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.

Risk factors and biomarkers of age-related macular degeneration

“…When at least one CFH risk allele was present, the population-attributable risk for late AMD was 53 percent (Klein et al, 2013). The strong association with risk alleles of CFH rs1061170 has also been validated in recent studies (Babanejad et al, 2015; Fauser and Lambrou, 2015; Hautamaki et al, 2015). …”

“…Further genomic studies of this chromosome demonstrated two AMD susceptible loci. One is known as rs10490924, which lies within the gene LOC387715/ARMS2, now known as Age-Related Maculopathy Susceptibility 2 (ARMS2) (Hautamaki et al, 2015; Kanda et al, 2007; Shen et al, 2015). The other, rs11200638, lies within the promoter region of the gene known as High Temperature Requirement Factor A1 (HTRA1) gene (Dewan et al, 2006; Francis and Klein, 2011; Yang et al, 2006).…”

[Retracted] Bone Marrow Plasma Cytokine Signature Profiles in Severe Aplastic Anemia

“…ere have been few reports on the relationships between these cytokines/chemokines and age/gender except in several age-related diseases, such as exudative age-related macular degeneration and age-related vocal fold atrophy [25,26]. We have no specific explanation as to why the four cytokines and chemokines were related to age/gender.…”

Dissecting microRNA dysregulation in age‐related macular degeneration: new targets for eye gene therapy

“…In addition, a genetic variant of the IL‐8 promoter region was recently found associated with the earlier onset of exudative AMD (Hautamaki et al. ), thereby further implicating miRNAs to play important roles in the retina.…”