Studies Find Genetic Links to Macular Degeneration

Findings suggest association with LIPC gene in high-density lipoprotein cholesterol pathway

MONDAY, April 19 (HealthDay News) -- A variant in the hepatic lipase (LIPC) gene in the high-density lipoprotein cholesterol (HDL-C) pathway may be associated with advanced age-related macular degeneration (AMD), according to two studies published online April 12 in the Proceedings of the National Academy of Sciences.

Benjamin M. Neale, of the Massachusetts General Hospital in Boston, and colleagues analyzed data from a genome-wide association study comprising 979 cases of advanced AMD and 1,709 controls, along with replication in additional cohorts. The association with the LIPC gene was strongest for a functional promoter variant that affects LIPC expression and serum HDL levels. However, the LIPC association may not be due to an effect on HDL levels, the researchers write.

Wei Chen, of the University of Michigan in Ann Arbor, and colleagues analyzed data from several groups of AMD cases and controls. Their findings validated disease susceptibility loci near CFH, ARMS2, C2/CFB, C3 and CFI, and identified a susceptibility locus near TIMP3. The researchers also found strong association signals with alleles at LIPC and CETP, which have been linked to blood levels of HDL-C, and an association between the disease and HDL-C-associated alleles near LPL and ABCA1.

"Although trends pointing to increased frequency of severe disease in individuals with high-risk genotypes should hold, the absolute risk of developing severe disease is difficult to estimate accurately in samples collected in tertiary clinics. In the meantime, our results point to new molecular pathways and encourage new directions in the search for treatment and prevention of this common blinding disease," Chen and colleagues conclude.

Tufts Medical Center and Massachusetts General Hospital have filed a patent application for materials related to the first article. Several authors of the second study are listed on patents related to genetic data in AMD, and a co-author disclosed financial relationships with Genentech and Pfizer.

Abstract - Neale
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Abstract - Chen
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