Plasma lipoprotein subfraction concentrations are associated with lipid metabolism and age-related macular degeneration[S]

Chui Ming Gemmy Cheung, Alfred Gan, Qiao Fan, Miao Ling Chee, Rajendra S. Apte, Chiea Chuen Khor, Ian Yeo, Ranjana Mathur, Ching-Yu Cheng, Tien Yin Wong, E. Shyong Tai

Disturbance in lipid metabolism has been suggested as a major pathogenic factor for age-related macular degeneration (AMD). Conventional lipid measures have been inconsistently associated with AMD. Other factors which can alter lipid metabolism include lipoprotein phenotype and genetic mutations. We performed a case-control study to examine the association between lipoprotein profile and neovascular AMD (nAMD), and whether the cholesterylester transfer protein CETP D442G mutation modulates these associations. Patients with nAMD had significantly higher concentrations of HDL and IDL lipoprotein compared to controls. The increase in HDL lipoprotein particles in nAMD patients was driven by an excess of medium-sized particles. Concurrently, patients with nAMD also had lower apolipoprotein A-1, lower VLDL and chylomicron lipoprotein. Many of these associations showed a dose dependent association between controls, early AMD cases and nAMD cases. Adjustment for the presence of the D442G mutation at the CETP locus did not significantly alter the increased AMD risk associated with HDL particle concentration. AMD is associated with variation in many lipoprotein subclasses, including increased in HDL particles and IDL particles, and decreased Apo A-1, VLDL and chylomicron particles. These suggest widespread systemic disturbance in lipid metabolism in the pathogenesis of AMD, including possible alterations in lipoprotein carrier capacity.