Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration: A Case-Control Study

Federico Ricci, Giovanni Staurenghi, Tiziana Lepre, Filippo Missiroli, Stefania Zampatti, Raffaella Cascella, Paola Borgiani, Luigi Tonino Marsella, Chiara Maria Eandi, Andrea Cusumano, Giuseppe Novelli, Emiliano Giardina

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Abstract

Background:Age-related macular degeneration (AMD) is the main cause of blindness in the developed world. The etiology of AMD is multifactorial due to the interaction between genetic and environmental factors. IL-8 has a role in inflammation and angiogenesis; we report the genetic characterization of IL-8 allele architecture and evaluate the role of SNPs or haplotypes in the susceptibility to wet AMD, case-control study.Methods:Case-control study including 721 AMD patients and 660 controls becoming from Italian population. Genotyping was carried out by Real Time-PCR. Differences in the frequencies were estimated by the chi-square test. Direct sequencing was carried out by capillary electrophoresis trough ABI3130xl.Results:rs2227306 showed a p-value of 4.15*10-5 and an Odds Ratio (OR) for T allele of 1.39 [1.19-1.62]. After these positive results, we sequenced the entire IL-8 regulatory and coding regions of 60 patients and 30 controls stratified for their genotype at rs2227306. We defined two different haplotypes involving rs4073 (A/T), rs2227306 (C/T), rs2227346 (C/T) and rs1126647 (A/T): A-T-T-T (p-value: 2.08*10-9; OR: 1.68 [1.43-1.97]) and T-C-C-A (p-value: 7.07*10-11; OR: 0.60 [0.51-0.70]). To further investigate a potential functional role of associated haplotypes, we performed an expression study on RNA extracted from whole blood of 75 donors to verify a possible direct correlation between haplotype and gene expression, failing to reveal significant differences.Conclusions:These results suggest a possible secondary role of IL-8 gene in the development of the disease. This paper outlines the importance of association between inflammation and AMD. Moreover IL-8 is a new susceptibility genomic biomarker of AMD.

Original languageEnglish
Article numbere66978
JournalPLoS One
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 19 2013

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Ricci, F., Staurenghi, G., Lepre, T., Missiroli, F., Zampatti, S., Cascella, R., Borgiani, P., Marsella, L. T., Eandi, C. M., Cusumano, A., Novelli, G., & Giardina, E. (2013). Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration: A Case-Control Study. PLoS One, 8(6), [e66978]. https://doi.org/10.1371/journal.pone.0066978