Human Molecular Genetics Advance Access published online on June 25, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm164
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Complement Factor H and Hemicentin-1 in Age-Related Macular Degeneration and Renal Phenotypes
1 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, 44106, USA 2 Department of Genetics, Case Western Reserve University, Cleveland, Ohio, 44106, USA 3 Department of Ophthalmology, Case Western Reserve University, Cleveland, Ohio, 44106, USA 4 Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin, 53706, USA
* Address correspondence to: Sudha K. Iyengar, Ph.D., Department of Epidemiology and Biostatistics, Case Western Reserve University, Wolstein Research Building Room 1315, 2103 Cornell Rd, Cleveland, OH 44106, Phone: (216) 368-5630, Fax: (216) 368-4880, e-mail: ski{at}case.edu
Received May 6, 2007; Revised June 21, 2007; Accepted June 21, 2007
In this study, we investigated the associations of Complement Factor H (CFH) and Hemicentin-1 (HMCN1) with age-related macular degeneration (AMD) and renal function. Three scales measuring the course of AMD and drusen development were examined in two samples: the Family Age Related Macular degeneration Study (FARMS), consisting of families ascertained through a single individual with severe AMD, and an unascertained population-based family cohort, the Beaver Dam Eye Study (BDES), which was also used to assess longitudinal changes in AMD and associations with renal function. Associations were performed via a regression accounting for known risk factors as well as familial and sibling effects.
Strong evidence of the association of the rs1061170 (Y402H) variation with AMD was confirmed (p = 9.15 x10–5 in BDES, p = 0.016 in FARMS). This association was observed in multiple AMD scales, suggesting its role is not phenotype specific. Polymorphisms in both CFH and HMCN1 appeared to influence the longitudinal rate of change of AMD.
The rs1061170 polymorphism was also associated with a reduction in estimated glomerular filtration rate (eGFR) (p = 0.046). Another CFH polymorphism, rs800292, was similarly associated with eGFR (ß = -0.90, [p = 0.022]). Associations between rs743137 (p = 0.05) and rs680638 (p = 0.022) in HMCN1 with calculated creatinine clearance progression were also observed. Both genes appear to play a role in both AMD and renal pathophysiology. These findings support evidence for common pathways influencing ocular and renal function and suggest that further work is needed on their common determinants.
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