Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in age-related macular degeneration (AMD)

Hum Mutat. 2007 Apr;28(4):406-13. doi: 10.1002/humu.20464.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Case-Control Studies
  • Conserved Sequence
  • Cysteine Endopeptidases / genetics*
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Haplotypes
  • Humans
  • Immunoglobulins / genetics*
  • Macular Degeneration / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • Protein Structure, Tertiary
  • Sequence Alignment


  • Extracellular Matrix Proteins
  • HMCN1 protein, human
  • Immunoglobulins
  • Cysteine Endopeptidases