HEMICENTIN-1 (FIBULIN-6) and the 1q31 AMD locus in the context of complex disease: review and perspective.
Age-related macular degeneration (AMD) is the most common blinding disorder in the Western world. Similar to other common diseases in which age is a risk factor (e.g., type II diabetes or Alzheimer's disease), AMD is thought to have a complex etiology. Previously, a Gln5345Arg mutation in HEMICENTIN-1 was found to segregate with AMD in a large family. However, the population frequency of this allele is inconsistent with the large proportion of families shown by linkage studies to map near this gene at 1q31. This review summarizes current knowledge regarding the role of HEMICENTIN-1 in AMD, the results of association studies for the Gln5345Arg mutation, and the linkage evidence for an AMD locus on 1q31. The data can be reconciled through proposing both additional variants in HEMICENTIN-1 and a second genetic risk factor for AMD in the region.
Schultz
Dennis W
DW
Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Boulevard, Portland, OR 97239-4197, U.S.A. schultzd@ohsu.edu
Weleber
Richard G
RG
Lawrence
Gus
G
Barral
Sandra
S
Majewski
Jacek
J
Acott
Ted S
TS
Klein
Michael L
ML
D000375:Aging / Q000502:physiology*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins; D008268:Macular Degeneration / Q000235:genetics*
D016326:Extracellular Matrix Proteins; C488168:HMCN1 protein, human; D007136:Immunoglobulins