Ophthalmology
Volume 117, Issue 8 , Pages 1560-1566, August 2010

C-Reactive Protein and CFH, ARMS2/HTRA1 Gene Variants Are Independently Associated with Risk of Macular Degeneration

  • Johanna M. Seddon, MD, ScM

      Affiliations

    • Ophthalmic Epidemiology and Genetics Service, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts
    • Corresponding Author InformationCorrespondence: Johanna M. Seddon, MD, Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, 800 Washington St., #450, Boston, MA 02111
    • ,
  • Gary Gensler, MS

      Affiliations

    • The EMMES Corporation, Rockville, Maryland
    • ,
  • Bernard Rosner, PhD

      Affiliations

    • Channing Laboratory, Harvard Medical School, Boston, Massachusetts

Received 27 July 2009; received in revised form 20 October 2009; accepted 12 November 2009. published online 26 March 2010.

Available online: March 26, 2010.

Purpose

Genetic variants CFH and ARMS2/HTRA1 gene regions as well as high-sensitivity C-reactive protein (CRP) levels are related to age-related macular degeneration (AMD). We evaluated their independent and combined effects on risk of AMD, as well as their interactions.

Design

Case-control study.

Participants

Subjects with AMD (n = 244) or no or minimal maculopathy (n = 209) in the Age Related Eye Disease Ancillary Study.

Methods

Risk factors, genotypes, and biomarkers were assessed by questionnaire, direct measurement, and analyses of blood specimens. The independent and joint effects of serum CRP and CFH (rs1061170) and ARMS2/HTRA1 (rs10490924) genotypes were assessed using logistic regression analyses, adjusting for age, gender, education, smoking, body mass index, and vitamin/mineral supplementation.

Main Outcome Measures

We defined AMD as large drusen, geographic atrophy, or neovascular disease.

Results

Higher CRP levels were associated with a higher risk of AMD, controlling for genotype and demographic and behavioral risk factors, with odds ratio 2.6 for levels of 3.0 mg/L and above versus below 1.0 mg/L (95% confidence interval, 1.01–6.7). Single nucleotide polymorphisms (SNPs) in both genes were also independently associated with risk of AMD, controlling for the level of CRP and other factors. Presence of both highest level of CRP together with risk genotypes for both SNPs, conferred the highest risk of AMD (OR 5.4, 95% CI 1.4-21.1).

Conclusions

High-sensitivity CRP and polymorphisms in the CFH and ARMS2/HTRA1 genes are independently associated with risk of AMD. Higher CRP level tends to confer a higher risk of AMD within most genotype groups.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

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 Manuscript no. 2009-1008.

 Financial Disclosure(s): The authors have made the following disclosures:

 Johanna Seddon - Tufts Medical Center - patent; Genentech – financial support.

 Supported by grants from the National Institutes of Health (NIH) National Eye Institute R01-EY11309; Massachusetts Lions Eye Research Fund, Inc, Northboro, MA; Individual Research Grant from Genentech, Inc.; and the Macular Degeneration Research Fund, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine.

PII: S0161-6420(09)01334-7

doi:10.1016/j.ophtha.2009.11.020

Ophthalmology
Volume 117, Issue 8 , Pages 1560-1566, August 2010

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