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

Research output: Contribution to journalArticle

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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interleukin-8
Macular Degeneration
case-control studies
Interleukin-8
Haplotypes
Case-Control Studies
haplotypes
Genes
odds ratio
genes
Odds Ratio
inflammation
Capillary electrophoresis
Alleles
Inflammation
alleles
Biomarkers
Gene expression
blindness
capillary electrophoresis

ASJC Scopus subject areas

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

Cite this

Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration : A Case-Control Study. / Ricci, Federico; Staurenghi, Giovanni; Lepre, Tiziana; Missiroli, Filippo; Zampatti, Stefania; Cascella, Raffaella; Borgiani, Paola; Marsella, Luigi Tonino; Eandi, Chiara Maria; Cusumano, Andrea; Novelli, Giuseppe; Giardina, Emiliano.

In: PLoS One, Vol. 8, No. 6, e66978, 19.06.2013.

Research output: Contribution to journalArticle

Ricci, F, Staurenghi, G, Lepre, T, Missiroli, F, Zampatti, S, Cascella, R, Borgiani, P, Marsella, LT, Eandi, CM, 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, vol. 8, no. 6, e66978. https://doi.org/10.1371/journal.pone.0066978
Ricci F, Staurenghi G, Lepre T, Missiroli F, Zampatti S, Cascella R et al. Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration: A Case-Control Study. PLoS One. 2013 Jun 19;8(6). e66978. https://doi.org/10.1371/journal.pone.0066978
Ricci, Federico ; Staurenghi, Giovanni ; Lepre, Tiziana ; Missiroli, Filippo ; Zampatti, Stefania ; Cascella, Raffaella ; Borgiani, Paola ; Marsella, Luigi Tonino ; Eandi, Chiara Maria ; Cusumano, Andrea ; Novelli, Giuseppe ; Giardina, Emiliano. / Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration : A Case-Control Study. In: PLoS One. 2013 ; Vol. 8, No. 6.
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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.",
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AU - Ricci, Federico

AU - Staurenghi, Giovanni

AU - Lepre, Tiziana

AU - Missiroli, Filippo

AU - Zampatti, Stefania

AU - Cascella, Raffaella

AU - Borgiani, Paola

AU - Marsella, Luigi Tonino

AU - Eandi, Chiara Maria

AU - Cusumano, Andrea

AU - Novelli, Giuseppe

AU - Giardina, Emiliano

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N2 - 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.

AB - 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.

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