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J. Gu, U. Narendra, G. Pauer, P. Nerone, S. Bamba, X. Yue, R. G. Salomon, S. A. Hagstrom, J. W. Crabb, Cleveland AMD Study Group; Plasma Carboxyethylpyrrole and AMD Risk Genotypes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5161.
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To evaluate how plasma levels of carboxyethylpyrrole (CEP) adducts and autoantibodies in patients with age-related macular degeneration (AMD) correlate with risk genotypes for AMD.
Blood was collected from clinically documented AMD and age-matched normal, healthy donors at the Cole Eye Institute, Cleveland Clinic Foundation and Louis Stokes Cleveland VA Medical Center. Plasma CEP and CEP autoantibody titer were determined by ELISA. DNA from blood donors was genotyped by either direct sequencing or restriction analysis for select risk polymorphisms associated with AMD, including Y402H in complement factor H (CFH), R80G in complement C3, A69S in LOC387715, and SNP rs11200638 in the promoter region of HTRA serine protease 1(HTRA1). Odds ratios for elevated CEP adducts and autoantibodies were calculated with SAS 9.1 software for homozygous and heterozygous genotypes relative to the wildtype genotype.
ELISA analyses of plasma from AMD donors (n = 902) demonstrated ~50% higher mean levels of CEP immunoreactivity and ~30% higher CEP autoantibody titer relative to age-matched control donors (n = 436). Genotyping has currently been completed on 529-541 AMD plasma donors. Odds ratios for elevated CEP were as follows: CFH (ORhomo=1.5, ORhet=1.0, n = 529 AMD plasma); HTRA1 (ORhomo=1.9, ORhet=1.3, n = 537 AMD plasma); LOC387715 (ORhomo=2.0, ORhet=1.2, n = 541 AMD plasma) and complement C3 (ORhomo=0.8, ORhet=1.1, n = 532 AMD plasma).
The odds of both CEP adducts and autoantibodies being elevated in AMD plasma appears to be higher for individuals homozygous for the CFH Y402H, HTRA1 and LOC 387715 risk polymorphisms for AMD. A combination of genotyping and CEP plasma may prove useful for monitoring AMD therapeutic efficacy.
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