title: Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in age-related macular degeneration (AMD).
abstract: This article reports a well-powered age-related macular degeneration (AMD) case-control association study in the HMCN1 gene, showing that common variants do not account for a substantial proportion of AMD cases. Thus, the consistent linkage peak observed by several genome-wide linkage scans within the 1q32 region is unlikely to be attributed to polymorphisms at the HMCN1 locus. In addition, the analysis provides comprehensive data suggesting that low-frequency variants encoding possible functional amino acid polymorphisms in the HMCN1 gene may not contribute substantially to disease, although HMCN1 mutations may still confer disease susceptibility in a small subset of patients. Interestingly, the HMCN1 p.Gln5346Arg mutation, which is thought to be a causal mutation in a large AMD pedigree segregating the disease as a single-gene trait, appears to occur in our control cohort as a low-frequency polymorphism with an allele frequency of approximately 0.0026.
authors.affiliation: Department of Medical and Molecular Genetics, Guy's King's and St Thomas' School of Medicine, King's College London, London, United Kingdom.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Fisher
authors.forename: Andrea
authors.initials: A
authors.lastname: Rivera
authors.forename: Lars G
authors.initials: LG
authors.lastname: Fritsche
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Keilhauer
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Günther
authors.initials: G
authors.lastname: Rudolph
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D016326:Extracellular Matrix Proteins; C488168:HMCN1 protein, human; D007136:Immunoglobulins; D003546:Cysteine Endopeptidases