title: Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration: A Case-Control Study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: UOSD Patologia retinica Fondazione PTV "Policlinico Tor Vergata", Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Ricci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Staurenghi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lepre
authors.forename: Filippo
authors.initials: F
authors.lastname: Missiroli
authors.forename: Stefania
authors.initials: S
authors.lastname: Zampatti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cascella
authors.forename: Paola
authors.initials: P
authors.lastname: Borgiani
authors.forename: Luigi Tonino
authors.initials: LT
authors.lastname: Marsella
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Eandi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cusumano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giardina
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8