Burdon Kathryn P, Hewitt Alex W, Mackey David A, Mitchell Paul, Craig Jamie E
Department of Ophthalmology, Flinders University, Adelaide, Australia.
Mol Vis. 2010 Nov 4;16:2286-93.
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.
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.
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.
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.
细胞色素P450家族1亚家族B（CYP1B1）基因是常染色体隐性原发性先天性青光眼的一个众所周知的病因。它也被假定为原发性开角型青光眼（POAG）疾病严重程度的一个修饰因子，特别是在青少年发病的家族中。然而，该基因常见变异与POAG的关系尚未得到充分研究。
对860例POAG患者和898例正常对照者进行基因分型，检测7个标签单核苷酸多态性（SNP），包括2个编码变异（L432V和N543S）。评估每个SNP和单倍型与疾病的相关性。此外，对396例重症患者和452例老年对照者进行了单独分析。
在完整数据集中，任何单个SNP均无相关性。在重症患者中，两个SNP（rs162562和rs10916）在显性模型下名义上具有相关性（p<0.05）。还发现一个常见单倍型（AGCAGCC）在完整数据集中名义上具有相关性（p=0.048，OR[95%CI]=0.83[0.69-0.90]），在重症患者中相关性更显著（p=0.004，OR[95%CI]=0.68[0.52-0.89]），经多重检验校正后仍具有统计学意义。
虽然未发现CYP1B1基因座常见变异对POAG有主要影响，但rs162562标记的SNP以及AGCAGCC单倍型可能存在影响。
