PURPOSE: To determine whether variants in the candidate genes TLR4, CCL2, and CCR2 are associated with age-related macular degeneration (AMD). METHODS: This study was performed in two independent Caucasian populations that included 357 cases and 173 controls from the Netherlands and 368 cases and 368 controls from the United States. Exon 4 of the TLR4 gene and the promoter, all exons, and flanking intronic regions of the CCL2 and CCR2 genes were analyzed in the Dutch study and common variants were validated in the U.S. study. Quantitative (q)PCR reactions were performed to evaluate expression of these genes in laser-dissected retinal pigment epithelium from 13 donor AMD and 13 control eyes. RESULTS: Analysis of single nucleotide polymorphisms (SNPs) in the TLR4 gene did not show a significant association between D299G or T399I and AMD, nor did haplotypes containing these variants. Univariate analyses of the SNPs in CCL2 and CCR2 did not demonstrate an association with AMD. For CCR2, haplotype frequencies were not significantly different between cases and controls. For CCL2, one haplotype containing the minor allele of C35C was significantly associated with AMD (P = 0.03), but this did not sustain after adjustment for multiple testing (q = 0.30). Expression analysis did not demonstrate altered RNA expression of CCL2 and CCR2 in the retinal pigment epithelium from AMD eyes (for CCL2 P = 0.62; for CCR2 P = 0.97). CONCLUSIONS: No evidence was found of an association between TLR4, CCR2, and CCL2 and AMD, which implies that the common genetic variation in these genes does not play a significant role in the etiology of AMD.
PURPOSE: To determine whether variants in the candidate genes TLR4, CCL2, and CCR2 are associated with age-related macular degeneration (AMD). METHODS: This study was performed in two independent Caucasian populations that included 357 cases and 173 controls from the Netherlands and 368 cases and 368 controls from the United States. Exon 4 of the TLR4 gene and the promoter, all exons, and flanking intronic regions of the CCL2 and CCR2 genes were analyzed in the Dutch study and common variants were validated in the U.S. study. Quantitative (q)PCR reactions were performed to evaluate expression of these genes in laser-dissected retinal pigment epithelium from 13 donorAMD and 13 control eyes. RESULTS: Analysis of single nucleotide polymorphisms (SNPs) in the TLR4 gene did not show a significant association between D299G or T399I and AMD, nor did haplotypes containing these variants. Univariate analyses of the SNPs in CCL2 and CCR2 did not demonstrate an association with AMD. For CCR2, haplotype frequencies were not significantly different between cases and controls. For CCL2, one haplotype containing the minor allele of C35C was significantly associated with AMD (P = 0.03), but this did not sustain after adjustment for multiple testing (q = 0.30). Expression analysis did not demonstrate altered RNA expression of CCL2 and CCR2 in the retinal pigment epithelium from AMD eyes (for CCL2 P = 0.62; for CCR2 P = 0.97). CONCLUSIONS: No evidence was found of an association between TLR4, CCR2, and CCL2 and AMD, which implies that the common genetic variation in these genes does not play a significant role in the etiology of AMD.
Authors: G S Hageman; P J Luthert; N H Victor Chong; L V Johnson; D H Anderson; R F Mullins Journal: Prog Retin Eye Res Date: 2001-11 Impact factor: 21.198
Authors: N C Arbour; E Lorenz; B C Schutte; J Zabner; J N Kline; M Jones; K Frees; J L Watt; D A Schwartz Journal: Nat Genet Date: 2000-06 Impact factor: 38.330
Authors: J P Ioannidis; P S Rosenberg; J J Goedert; L J Ashton; T L Benfield; S P Buchbinder; R A Coutinho; J Eugen-Olsen; T Gallart; T L Katzenstein; L G Kostrikis; H Kuipers; L G Louie; S A Mallal; J B Margolick; O P Martinez; L Meyer; N L Michael; E Operskalski; G Pantaleo; G P Rizzardi; H Schuitemaker; H W Sheppard; G J Stewart; I D Theodorou; H Ullum; E Vicenzi; D Vlahov; D Wilkinson; C Workman; J F Zagury; T R O'Brien Journal: Ann Intern Med Date: 2001-11-06 Impact factor: 25.391
Authors: Ana M Valdes; Megan L Wolfe; Eamonn J O'Brien; Nigel K Spurr; Warren Gefter; Andrew Rut; Pieter H E Groot; Daniel J Rader Journal: Arterioscler Thromb Vasc Biol Date: 2002-11-01 Impact factor: 8.311
Authors: Enrique Gonzalez; Brad H Rovin; Luisa Sen; Glen Cooke; Rahul Dhanda; Srinivas Mummidi; Hemant Kulkarni; Michael J Bamshad; Vanessa Telles; Stephanie A Anderson; Elizabeth A Walter; Kevin T Stephan; Michael Deucher; Andrea Mangano; Rosa Bologna; Seema S Ahuja; Matthew J Dolan; Sunil K Ahuja Journal: Proc Natl Acad Sci U S A Date: 2002-10-08 Impact factor: 11.205
Authors: Jayakrishna Ambati; Akshay Anand; Stefan Fernandez; Eiji Sakurai; Bert C Lynn; William A Kuziel; Barrett J Rollins; Balamurali K Ambati Journal: Nat Med Date: 2003-10-19 Impact factor: 53.440
Authors: Jo Vandesompele; Katleen De Preter; Filip Pattyn; Bruce Poppe; Nadine Van Roy; Anne De Paepe; Frank Speleman Journal: Genome Biol Date: 2002-06-18 Impact factor: 13.583
Authors: Alexandra C Silveira; Margaux A Morrison; Fei Ji; Haiyan Xu; James B Reinecke; Scott M Adams; Trevor M Arneberg; Maria Janssian; Joo-Eun Lee; Yang Yuan; Debra A Schaumberg; Maria G Kotoula; Evangeline E Tsironi; Aristoteles N Tsiloulis; Dimitrios Z Chatzoulis; Joan W Miller; Ivana K Kim; Gregory S Hageman; Lindsay A Farrer; Neena B Haider; Margaret M DeAngelis Journal: Vision Res Date: 2009-09-26 Impact factor: 1.886
Authors: Youngeun Cho; Jie Jin Wang; Emily Y Chew; Frederick L Ferris; Paul Mitchell; Chi-Chao Chan; Jingsheng Tuo Journal: Invest Ophthalmol Vis Sci Date: 2009-07-23 Impact factor: 4.799