September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Dyslipidemia and Lipoprotein Profile in Age-related Macular Degeneration
Author Affiliations & Notes
  • Gemmy Cheung
    Singapore National Eye Center, Singapore, Singapore
    Singapore Eye Research Institute, Singapore, Singapore
  • Alfred Tau Liang Gan
    Singapore Eye Research Institute, Singapore, Singapore
  • Qiao Fan
    Singapore Eye Research Institute, Singapore, Singapore
  • Rajendra S Apte
    Washington University, St Louis, Montana, United States
  • Shyam Chaurasia
    Singapore Eye Research Institute, Singapore, Singapore
  • Ching-Yu Cheng
    Singapore Eye Research Institute, Singapore, Singapore
  • Tien Yin Wong
    Singapore National Eye Center, Singapore, Singapore
    Singapore Eye Research Institute, Singapore, Singapore
  • E Shyong Tai
    National University of Singapore, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Gemmy Cheung, None; Alfred Tau Liang Gan, None; Qiao Fan, None; Rajendra Apte, None; Shyam Chaurasia, None; Ching-Yu Cheng, None; Tien Wong, None; E Shyong Tai, None
  • Footnotes
    Support  National Medical Research Council grant NMRC/NIG/1003/2009 and Biomedical Research Council grant BMRC 10/1/35/19/671
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2124. doi:
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      Gemmy Cheung, Alfred Tau Liang Gan, Qiao Fan, Rajendra S Apte, Shyam Chaurasia, Ching-Yu Cheng, Tien Yin Wong, E Shyong Tai; Dyslipidemia and Lipoprotein Profile in Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2124.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : We recently identified a mutation (D442G) at the cholesteryl ester transfer protein (CETP) locus associated with elevated HDL-C and late AMD. We now examine the association between lipoprotein particle size distribution and AMD, and whether CETP D442G mutation may modulate this association.

Methods : We performed a case-control study of AMD cases (184 early AMD; 193 exudative AMD) and 289 age and gender-matched controls. Serum was analyzed for lipid biochemistry and lipoprotein particle concentrations, particle size and subfractions with nuclear magnetic resonance spectroscopy. CETP status was determined using Illumina Human OmniExpress or Taqman probe. Serum CETP activity was measured using Elisa.

Results : HDL-C was higher in exudative AMD cases (1.4mmol/L) than controls (1.3mmol/L, p=0.027) and early AMD cases (1.3mmol/L, p=0.067). There were marked differences in the lipoprotein particle profile between the exudative AMD group and controls, with higher concentrations of HDL particles (37.2 vs 35.3 µmol/L, p=0.039), and intermediate-density lipoprotein (IDL) particles (155.6 vs 110.7nmol/L, p<0.001), and lower concentrations of VLDL particles (60.6 vs 73.2 nmol/L, p<0.001) and ApoA1 (145.3 vs 155.8, p<0.001). Mean HDL particle size was larger in exudative AMD cases than controls (9.3 vs 9.2 nm, p=0.01). After multivariable adjustment, each unit increase in HDL particles was associated with a 5% increase in exudative AMD risk (p=0.002). Early AMD cases only had few differences in lipoprotein profile compared to controls. CETP activity was not significantly different between the two groups. Adjustment for the presence of CETP D442G polymorphism did not significantly alter the associations; however, there was a statistically significant interaction between CETP D442G polymorphism and HDL-particle number and exudative AMD.

Conclusions : Patients with exudative AMD have a distinct lipoprotein profile. These findings were not mediated by the CETP D442G mutation, but suggest more widespread disturbance in lipid metabolism in exudative AMD. Lower ApoA1 could correlate with impaired reverse cholesterol transport by causing impaired lipid carrier capacity. Lipoprotein profile in early AMD cases was largely similar to controls, suggestig that lipid metabolism may affect pathways responsible for progression from early to exudative AMD. Modulation of lipid metabolism may represent a novel means to retard the development of AMD.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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