Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes.

Kleins Lab // Publications // Sep 01 2007

PubMed ID: 17591627

Author(s): Thompson CL, Klein BE, Klein R, Xu Z, Capriotti J, Joshi T, Leontiev D, Lee KE, Elston RC, Iyengar SK. Complement factor H and hemicentin-1 in age-related macular degeneration and renal phenotypes. Hum Mol Genet. 2007 Sep 1;16(17):2135-48. Epub 2007 Jun 25. PMID 17591627

Journal: Human Molecular Genetics, Volume 16, Issue 17, Sep 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 by a regression accounting for known risk factors as well as familial and sibling effects. Strong evidence of the association of rs1061170 (Y402H) variation with AMD was confirmed (P = 9.15 x 10(-5) in BDES, P = 0.016 in FARMS). This association was observed in multiple AMD scales, suggesting that 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 [beta = -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 required on their common determinants.