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 language | English |
|---|---|
| Article number | e66978 |
| Journal | PLoS One |
| Volume | 8 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 19 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration
T2 - A Case-Control Study
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
PY - 2013/6/19
Y1 - 2013/6/19
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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U2 - 10.1371/journal.pone.0066978
DO - 10.1371/journal.pone.0066978
M3 - Article
AN - SCOPUS:84879224300
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e66978
ER -