Purpose: The cytochrome p450 family 1 subfamily B (CYP1B1) gene is a well known cause of autosomal recessive primary congenital glaucoma. It has also been postulated as a modifier of disease severity in primary open angle glaucoma (POAG), particularly in juvenile onset families. However, the role of common variation in the gene in relation to POAG has not been thoroughly explored.
Methods: Seven tag single nucleotide polymorphisms (SNPs), including two coding variants (L432V and N543S), were genotyped in 860 POAG cases and 898 examined normal controls. Each SNP and haplotype was assessed for association with disease. In addition, a subset of 396 severe cases and 452 elderly controls were analyzed separately.
Results: There was no association of any individual SNP in the full data set. Two SNPs (rs162562 and rs10916) were nominally associated under a dominant model in the severe cases (p<0.05). A common haplotype (AGCAGCC) was also found to be nominally associated in both the full data set (p=0.048, OR [95%CI]=0.83 [0.69-0.90]) and more significantly in the severe cases (p=0.004, OR [95%CI]=0.68 [0.52-0.89]) which survives correction for multiple testing.
Conclusions: Although no major effect of common variation at the CYP1B1 locus on POAG was found, there could be an effect of SNPs tagged by rs162562 and represented on the AGCAGCC haplotype.