VAMP5 and VAMP8 are most likely not involved in primary open-angle glaucoma.
OBJECTIVE
To select and characterize novel POAG disease genes. On the basis of genetic position (GLC1B), expression in the optic nerve, and biochemical function (targeted membrane transport processes), we selected the human VAMP5 and VAMP8 (encoding vesicle-associated membrane proteins 5 and 8) as potential candidate disease genes for POAG. We subsequently analyzed whether or not sequence changes in VAMP5 or VAMP8 were implicated in POAG.


METHODS
Genomic DNA samples from 90 POAG cases and 60 controls were screened by denaturing high performance liquid chromatography of fragments amplified by the polymerase chain reaction. Direct sequencing identified nucleotide changes.


RESULTS
No nonsynonymous rare sequence variants were found in VAMP5 or VAMP8. In VAMP5, three previously identified and five new single nucleotide polymorphisms (SNPs) were found. In VAMP8, four known and two new SNPs were detected. All new SNPs did not appear to change gene function or alter gene splicing. No significant differences were found between the allele frequencies in POAG cases and controls.


CONCLUSIONS
Our findings indicate that VAMP5 and VAMP8 are not involved in POAG in the Dutch population.
Brinkman
Joep F F
JF
Division of Development, Aging and Genetic diseases of the Eye, Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Ophthalmic Research Institute, The Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Ottenheim
Cecile P E
CP
de Jong
Leo A M S
LA
Zegers
Richard H C
RH
de Smet
Marc D
MD
de Jong
Paulus T V M
PT
Bergen
Arthur A B
AA
D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005091:Exons / Q000235:genetics; D008040:Genetic Linkage; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D050683:R-SNARE Proteins / Q000235:genetics*
D017931:DNA Primers; D050683:R-SNARE Proteins; C485545:VAMP5 protein, human; C112938:VAMP8 protein, human