PURPOSE: Identification of genetic factors for age-related macular degeneration (AMD) is of crucial importance in this common cause of blindness. Exudative AMD is rapidly progressive and usually associated with severe prognosis. Our purpose was to investigate this association on locus 10q26 in a case-control study including French patients specifically affected with exudative AMD. METHODS: Polymorphisms rs4146894:G>A of Pleckstrin Homology Domain-containing Protein Family A member 1 (PLEKHA1) gene, rs10490924:G>T at LOC387715, and rs11200638:G>A of HTRA1 (HTRA serine peptidase 1) gene were analyzed in AMD cases (n=118, age=72.3+/-3.8 years old) and healthy controls (n=116, age=72.0+/-3.8 years old). RESULTS: PLEKHA1 polymorphism was associated with AMD. The A allele frequency was 0.67 in cases versus 0.41 in controls, (p=0.0001). After age and sex adjustment, the odds ratio for risk of AMD was 9.1 (4.0-20.9, 95% CI, p=0.0001) for the AA genotype and 2.6 (1.3-5.5, 95% CI, p=0.04) for the AG genotype, conditional on HTRA1. Association was even stronger and independent with HTRA1. The A allele frequency was 0.51 in cases versus 0.22 in controls, (p=0.0001). The odds ratio was 15.5 (5.5-43.9, 95% CI, p=0.0001) for the AA genotype and 3.4 (1.9-6.1, 95% CI, p=0.0001) for the AG genotype. No further information was obtained from LOC387715 due to virtually complete linkage disequilibrium with HTRA1 polymorphism in cases (D'=1.0) and controls (D'=0.98). Although a role for PLEKHA1 could not be totally excluded, there was a four times higher AMD risk was associated with haplotype "A-T-A" involving "PLEKHA1-LOC387715-HTRA1" risk alleles. CONCLUSIONS: Compared to PLEKHA1, HTRA1/LOC387715 genetic variations were independently and strongly associated with exudative AMD in the French population. Chromosome-10 genetic variants appear as potentially useful risk markers for early detection of AMD.
PURPOSE: Identification of genetic factors for age-related macular degeneration (AMD) is of crucial importance in this common cause of blindness. Exudative AMD is rapidly progressive and usually associated with severe prognosis. Our purpose was to investigate this association on locus 10q26 in a case-control study including French patients specifically affected with exudative AMD. METHODS: Polymorphisms rs4146894:G>A of Pleckstrin Homology Domain-containing Protein Family A member 1 (PLEKHA1) gene, rs10490924:G>T at LOC387715, and rs11200638:G>A of HTRA1 (HTRA serine peptidase 1) gene were analyzed in AMD cases (n=118, age=72.3+/-3.8 years old) and healthy controls (n=116, age=72.0+/-3.8 years old). RESULTS:PLEKHA1 polymorphism was associated with AMD. The A allele frequency was 0.67 in cases versus 0.41 in controls, (p=0.0001). After age and sex adjustment, the odds ratio for risk of AMD was 9.1 (4.0-20.9, 95% CI, p=0.0001) for the AA genotype and 2.6 (1.3-5.5, 95% CI, p=0.04) for the AG genotype, conditional on HTRA1. Association was even stronger and independent with HTRA1. The A allele frequency was 0.51 in cases versus 0.22 in controls, (p=0.0001). The odds ratio was 15.5 (5.5-43.9, 95% CI, p=0.0001) for the AA genotype and 3.4 (1.9-6.1, 95% CI, p=0.0001) for the AG genotype. No further information was obtained from LOC387715 due to virtually complete linkage disequilibrium with HTRA1 polymorphism in cases (D'=1.0) and controls (D'=0.98). Although a role for PLEKHA1 could not be totally excluded, there was a four times higher AMD risk was associated with haplotype "A-T-A" involving "PLEKHA1-LOC387715-HTRA1" risk alleles. CONCLUSIONS: Compared to PLEKHA1, HTRA1/LOC387715 genetic variations were independently and strongly associated with exudative AMD in the French population. Chromosome-10 genetic variants appear as potentially useful risk markers for early detection of AMD.
Authors: Giuseppe Querques; Bénédicte M J Merle; Nicole M Pumariega; Pascale Benlian; Cécile Delcourt; Alain Zourdani; Heather B Leisy; Michele D Lee; R Theodore Smith; Eric H Souied Journal: PLoS One Date: 2016-02-22 Impact factor: 3.240
Authors: Daniel I Chasman; Christian Fuchsberger; Cristian Pattaro; Alexander Teumer; Carsten A Böger; Karlhans Endlich; Matthias Olden; Ming-Huei Chen; Adrienne Tin; Daniel Taliun; Man Li; Xiaoyi Gao; Mathias Gorski; Qiong Yang; Claudia Hundertmark; Meredith C Foster; Conall M O'Seaghdha; Nicole Glazer; Aaron Isaacs; Ching-Ti Liu; Albert V Smith; Jeffrey R O'Connell; Maksim Struchalin; Toshiko Tanaka; Guo Li; Andrew D Johnson; Hinco J Gierman; Mary F Feitosa; Shih-Jen Hwang; Elizabeth J Atkinson; Kurt Lohman; Marilyn C Cornelis; Asa Johansson; Anke Tönjes; Abbas Dehghan; Jean-Charles Lambert; Elizabeth G Holliday; Rossella Sorice; Zoltan Kutalik; Terho Lehtimäki; Tõnu Esko; Harshal Deshmukh; Sheila Ulivi; Audrey Y Chu; Federico Murgia; Stella Trompet; Medea Imboden; Stefan Coassin; Giorgio Pistis; Tamara B Harris; Lenore J Launer; Thor Aspelund; Gudny Eiriksdottir; Braxton D Mitchell; Eric Boerwinkle; Helena Schmidt; Margherita Cavalieri; Madhumathi Rao; Frank Hu; Ayse Demirkan; Ben A Oostra; Mariza de Andrade; Stephen T Turner; Jingzhong Ding; Jeanette S Andrews; Barry I Freedman; Franco Giulianini; Wolfgang Koenig; Thomas Illig; Christa Meisinger; Christian Gieger; Lina Zgaga; Tatijana Zemunik; Mladen Boban; Cosetta Minelli; Heather E Wheeler; Wilmar Igl; Ghazal Zaboli; Sarah H Wild; Alan F Wright; Harry Campbell; David Ellinghaus; Ute Nöthlings; Gunnar Jacobs; Reiner Biffar; Florian Ernst; Georg Homuth; Heyo K Kroemer; Matthias Nauck; Sylvia Stracke; Uwe Völker; Henry Völzke; Peter Kovacs; Michael Stumvoll; Reedik Mägi; Albert Hofman; Andre G Uitterlinden; Fernando Rivadeneira; Yurii S Aulchenko; Ozren Polasek; Nick Hastie; Veronique Vitart; Catherine Helmer; Jie Jin Wang; Bénédicte Stengel; Daniela Ruggiero; Sven Bergmann; Mika Kähönen; Jorma Viikari; Tiit Nikopensius; Michael Province; Shamika Ketkar; Helen Colhoun; Alex Doney; Antonietta Robino; Bernhard K Krämer; Laura Portas; Ian Ford; Brendan M Buckley; Martin Adam; Gian-Andri Thun; Bernhard Paulweber; Margot Haun; Cinzia Sala; Paul Mitchell; Marina Ciullo; Stuart K Kim; Peter Vollenweider; Olli Raitakari; Andres Metspalu; Colin Palmer; Paolo Gasparini; Mario Pirastu; J Wouter Jukema; Nicole M Probst-Hensch; Florian Kronenberg; Daniela Toniolo; Vilmundur Gudnason; Alan R Shuldiner; Josef Coresh; Reinhold Schmidt; Luigi Ferrucci; David S Siscovick; Cornelia M van Duijn; Ingrid B Borecki; Sharon L R Kardia; Yongmei Liu; Gary C Curhan; Igor Rudan; Ulf Gyllensten; James F Wilson; Andre Franke; Peter P Pramstaller; Rainer Rettig; Inga Prokopenko; Jacqueline Witteman; Caroline Hayward; Paul M Ridker; Afshin Parsa; Murielle Bochud; Iris M Heid; W H Linda Kao; Caroline S Fox; Anna Köttgen Journal: Hum Mol Genet Date: 2012-09-08 Impact factor: 6.150
Authors: Paul P Connell; Pearse A Keane; Evelyn C O'Neill; Rasha W Altaie; Edward Loane; Kumari Neelam; John M Nolan; Stephen Beatty Journal: J Ophthalmol Date: 2009-09-06 Impact factor: 1.909
Authors: Jennyfer Zerbib; Florence Richard; Nathalie Puche; Nicolas Leveziel; Salomon Y Cohen; Jean-François Korobelnik; José Sahel; Arnold Munnich; Josseline Kaplan; Jean-Michel Rozet; Eric H Souied Journal: Mol Vis Date: 2010-07-15 Impact factor: 2.367
Authors: Jennyfer Zerbib; Johanna M Seddon; Florence Richard; Robyn Reynolds; Nicolas Leveziel; Pascale Benlian; Patrick Borel; Josué Feingold; Arnold Munnich; Gisèle Soubrane; Josseline Kaplan; Jean-Michel Rozet; Eric H Souied Journal: PLoS One Date: 2009-10-05 Impact factor: 3.240