Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers

Jiayin Gu, Gayle J.T. Pauer, Xiuzhen Yue, Umadevi Narendra, Gwen M. Sturgill, James Bena, Xiaorong Gu, Neal S. Peachey, Robert G. Salomon, Stephanie A. Hagstrom, John W. Crabb, David Barnhart, William J. Dupps, Froncie A. Gutman, Peter K. Kaiser, Hilel Lewis, Richard E. Gans, Bennie H. Jeng, Gregory S. Kosmorsky, Ronald R Krueger & 19 others Ann Laurenzi, Roger H.S. Langston, Edward J. Rockwood, William E. Sax, Andrew P. Schachat, Jonathan E. Sears, Rishi Singh, Scott D. Smith, Mindy Toabe, Elias I. Traboulsi, Nadia Waheed, Steven E. Wilson, Stacia S. Yaniglos, Elisa Bala, Sonya Bamba, Sue Crowe, Patrice Nerone, Tiffany Ruez, Ellen Simpson

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Age-related macular degeneration (AMD) is a progressive disease and major cause of severe visual loss. Toward the discovery of tools for early identification of AMD susceptibility, we evaluated the combined predictive capability of proteomic and genomic AMD biomarkers. We quantified plasma carboxyethylpyrrole (CEP) oxidative protein modifications and CEP autoantibodies by ELISA in 916 AMD and 488 control donors. CEP adducts are uniquely generated from oxidation of docosahexaenoate-containing lipids that are abundant in the retina. Mean CEP adduct and autoantibody levels were found to be elevated in AMD plasma by ∼60 and ∼30%, respectively. The odds ratio for both CEP markers elevated was 3-fold greater or more in AMD than in control patients. Genotyping was performed for AMD risk polymorphisms associated with age-related maculopathy susceptibility 2 (ARMS2), high temperature requirement factor A1 (HTRA1), complement factor H, and complement C3, and the risk of AMD was predicted based on genotype alone or in combination with the CEP markers. The AMD risk predicted for those exhibiting elevated CEP markers and risk genotypes was 2-3-fold greater than the risk based on genotype alone. AMD donors carrying the ARMS2 and HTRA1 risk alleles were the most likely to exhibit elevated CEP markers. The results compellingly demonstrate higher mean CEP marker levels in AMD plasma over a broad age range. Receiver operating characteristic curves suggest that CEP markers alone can discriminate between AMD and control plasma donors with ∼76% accuracy and in combination with genomic markers provide up to ∼80% discrimination accuracy. Plasma CEP marker levels were altered slightly by several demographic and health factors that warrant further study. We conclude that CEP plasma biomarkers, particularly in combination with genomic markers, offer a potential early warning system for assessing susceptibility to this blinding, multifactorial disease.

Original languageEnglish (US)
Pages (from-to)1338-1349
Number of pages12
JournalMolecular and Cellular Proteomics
Volume8
Issue number6
DOIs
StatePublished - Jun 1 2009

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Macular Degeneration
Biomarkers
Proteomics
Plasmas
Autoantibodies
Complement Factor H
Complement C3
Docosahexaenoic Acids
Alarm systems
Genotype
Tissue Donors
Polymorphism
Health
Lipids
Oxidation
Temperature
ROC Curve
Retina
Proteins
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Cite this

Gu, J., Pauer, G. J. T., Yue, X., Narendra, U., Sturgill, G. M., Bena, J., ... Simpson, E. (2009). Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers. Molecular and Cellular Proteomics, 8(6), 1338-1349. https://doi.org/10.1074/mcp.M800453-MCP200

Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers. / Gu, Jiayin; Pauer, Gayle J.T.; Yue, Xiuzhen; Narendra, Umadevi; Sturgill, Gwen M.; Bena, James; Gu, Xiaorong; Peachey, Neal S.; Salomon, Robert G.; Hagstrom, Stephanie A.; Crabb, John W.; Barnhart, David; Dupps, William J.; Gutman, Froncie A.; Kaiser, Peter K.; Lewis, Hilel; Gans, Richard E.; Jeng, Bennie H.; Kosmorsky, Gregory S.; Krueger, Ronald R; Laurenzi, Ann; Langston, Roger H.S.; Rockwood, Edward J.; Sax, William E.; Schachat, Andrew P.; Sears, Jonathan E.; Singh, Rishi; Smith, Scott D.; Toabe, Mindy; Traboulsi, Elias I.; Waheed, Nadia; Wilson, Steven E.; Yaniglos, Stacia S.; Bala, Elisa; Bamba, Sonya; Crowe, Sue; Nerone, Patrice; Ruez, Tiffany; Simpson, Ellen.

In: Molecular and Cellular Proteomics, Vol. 8, No. 6, 01.06.2009, p. 1338-1349.

Research output: Contribution to journalArticle

Gu, J, Pauer, GJT, Yue, X, Narendra, U, Sturgill, GM, Bena, J, Gu, X, Peachey, NS, Salomon, RG, Hagstrom, SA, Crabb, JW, Barnhart, D, Dupps, WJ, Gutman, FA, Kaiser, PK, Lewis, H, Gans, RE, Jeng, BH, Kosmorsky, GS, Krueger, RR, Laurenzi, A, Langston, RHS, Rockwood, EJ, Sax, WE, Schachat, AP, Sears, JE, Singh, R, Smith, SD, Toabe, M, Traboulsi, EI, Waheed, N, Wilson, SE, Yaniglos, SS, Bala, E, Bamba, S, Crowe, S, Nerone, P, Ruez, T & Simpson, E 2009, 'Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers', Molecular and Cellular Proteomics, vol. 8, no. 6, pp. 1338-1349. https://doi.org/10.1074/mcp.M800453-MCP200
Gu, Jiayin ; Pauer, Gayle J.T. ; Yue, Xiuzhen ; Narendra, Umadevi ; Sturgill, Gwen M. ; Bena, James ; Gu, Xiaorong ; Peachey, Neal S. ; Salomon, Robert G. ; Hagstrom, Stephanie A. ; Crabb, John W. ; Barnhart, David ; Dupps, William J. ; Gutman, Froncie A. ; Kaiser, Peter K. ; Lewis, Hilel ; Gans, Richard E. ; Jeng, Bennie H. ; Kosmorsky, Gregory S. ; Krueger, Ronald R ; Laurenzi, Ann ; Langston, Roger H.S. ; Rockwood, Edward J. ; Sax, William E. ; Schachat, Andrew P. ; Sears, Jonathan E. ; Singh, Rishi ; Smith, Scott D. ; Toabe, Mindy ; Traboulsi, Elias I. ; Waheed, Nadia ; Wilson, Steven E. ; Yaniglos, Stacia S. ; Bala, Elisa ; Bamba, Sonya ; Crowe, Sue ; Nerone, Patrice ; Ruez, Tiffany ; Simpson, Ellen. / Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers. In: Molecular and Cellular Proteomics. 2009 ; Vol. 8, No. 6. pp. 1338-1349.
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AU - Bena, James

AU - Gu, Xiaorong

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