Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA

Abstract

Primary open-angle glaucoma (POAG) is a genetically complex common disease characterized by progressive optic nerve degeneration that results in irreversible blindness. Recently, a genome-wide association study (GWAS) for POAG in an Icelandic population identified significant associations with single nucleotide polymorphisms (SNPs) between the CAV1 and CAV2 genes on chromosome 7q31. In this study, we confirm that the identified SNPs are associated with POAG in our Caucasian US population and that specific haplotypes located in the CAV1/CAV2 intergenic region are associated with the disease. We also present data suggesting that associations with several CAV1/CAV2 SNPs are significant mostly in women.

Figure 1.

The CAV1/CAV2 gene region. Depicted are predicted genes and splice variants for CAV1 and CAV2 as seen in the UCSC Genome browser. Genotyped SNPs passing quality-control measures (n= 63) that were not nominally significant in the case–control analysis are colored black. SNPs that were nominally significant are colored blue (0.01 < P< 0.05), orange (0.005 < P< 0.01) and red (P< 0.005).

Figure 2.

Pathways influencing vascular tone that include eNOS (NOS3), caveolin and estrogen receptors. The caveolin membrane refers to the side of the membrane bound to caveolin. E2, estrogen; Era, estrogen receptor A; Ga, guanine nucleotide-binding protein alpha; GBy, guanine nucleotide-binding protein beta/gamma; NO, nitric oxide; eNOS, endothelial nitric oxide synthase; Akt/PKB, v-akt murine thymoma viral oncogene homolog; TK, thymidine kinase; MAPK, mitogen-activated protein kinase; AMP-activ PK, AMP activated protein kinase; PKA, protein kinase A; PKC, protein kinase C; HPS90, heat-shock protein 90; CM, calmodulin; Ca++, calcium.