Mutation Screen in the VTN Gene in 188 Patients With Age–Related Macular Degeneration

Abstract

Purpose: : Vitronectin (VTN) is an adhesive glycoprotein that is present at high concentration in the plasma and is a common component of adult extracellular matrix. It is a principal component of Bruch’s membrane and is one of the most commonly encountered proteins in drusen isolated from AMD eyes. VTN is known to be expressed by photoreceptor and ganglion cells of the retina. In addition to its established role in mediating cell adhesion, VTN also has regulatory roles in several complement–mediated cell processes. For these reasons, we investigated VTN as a candidate gene for AMD.

Methods: : All eight coding exons of VTN have been screened for mutations in 188 unrelated patients with AMD using exon–by–exon SSCP. Variant bands were detected in exons 6, 7, and 8 and were further analyzed by direct genomic sequencing.

Results: : Three sequence changes (Arg323Arg, Thr400Met, Phe437Val) were identified in VTN. The Thr400Met missense change had an allele frequency of 49.1% in patients and was determined to be a non–pathogenic polymorphism. The Phe437Val missense change was identified heterozygously in one patient and had a minor allele frequency of 0.26%. It was not identified in 56 age–matched normal controls. Additional SSCP variant bands were identified in exons 6 and 8 and are currently being sequenced.

Conclusions: : To date, we report three sequence changes in VTN in patients with AMD; however, we are unable to associate these changes with disease. We are proceeding with an evaluation of the remaining variant bands identified in these patients and an evaluation of all exons in additional patients.

Keywords: age-related macular degeneration • gene screening • retinal degenerations: hereditary