Assessment of the contribution of the LOC387715 gene polymorphism in a family with exudative age-related macular degeneration and heterozygous CFH variant (Y402H)

Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly population in developed countries. The etiology of AMD is not completely understood but environmental and genetic factors have been implicated in the disease. Recently it has been documented that variations in the complement factor H (CFH) and LOC 387715 genes are the major risk factors that predispose individuals to dry and wet AMD. To investigate further the genetic contribution to AMD, we have analyzed the LOC 387715 gene in a non-smoking family with an exudative AMD and a heterozygous mutation (Y402H) in the CFH gene. Direct sequencing of the amplified product of exon 1 of the LOC 387715 gene identified a previously reported missense mutation (A69S) in this family. The affected individual is homozygous for the mutation and this sequence alteration was not identified in six age-matched controls. On the basis of this and other results it is tempting to speculate that the combined effect of variants in the CFH and LOC 387715 genes may contribute to the AMD phenotype in this family. Further studies on these and other susceptibility genes may provide clues on variable phenotypes, new preventive strategies and treatment options for AMD.