Chromosome 7q31 POAG locus: ocular expression of caveolins and lack of association with POAG in a US cohort
Chromosome 7q31 POAG locus: ocular expression of caveolins and lack of association with POAG in a US cohort
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发表时间：
2011-02
期刊：
影响因子：
2.2
通讯作者：
M. Kuehn;Kai Wang;B. Roos;E. Stone;Young H. Kwon;W. Alward;R. Mullins;J. Fingert
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作者：
M. Kuehn;Kai Wang;B. Roos;E. Stone;Young H. Kwon;W. Alward;R. Mullins;J. Fingert
目的探讨原发性开角型青光眼（primary open angle glaucoma，POAG）危险因子在爱荷华州青光眼患者染色体7 q31上的作用，并确定该基因在人眼中的表达模式。方法采用定量聚合酶链反应（PCR）方法对来自爱荷华州的545例POAG患者和297例对照者进行染色体7 q31位点单核苷酸多态性（SNP; rs 4236601）基因分型。应用免疫组织化学方法检测人眼内7 q31基因座Caveolin-1（CAV 1）和Caveolin-2（CAV 2）的表达。结果rs 4236601等位基因频率（MAF）在正常对照组和POAG组分别为27%和29%。当我们比较原发性开角型青光眼患者和对照组之间rs 4236601的等位基因频率时，我们没有发现统计学差异（p=0.5）。同样，我们检测到患者和对照组之间三种可能的rs 4236601基因型的频率没有统计学差异（p=0.22）。免疫组化显示窖蛋白在人视网膜、睫状肌、小梁网和Schlemm管中表达。在我们的小队列供体眼中，rs 4236601的基因型对视网膜中CAV 1和CAV 2的标记强度或分布没有明显影响。结论：对冰岛受试者进行的全基因组关联研究将POAG的第一个常见遗传风险因子定位于染色体7 q31上的一个小区域，该区域包含caveolin基因CAV 1和CAV 2。我们无法在来自爱荷华州的患者中检测到这种关联，这表明这种风险因素可能不会在所有人群中产生强烈影响。
Purpose To determine the role of the recently discovered primary open angle glaucoma (POAG) risk factor mapped to chromosome 7q31 in glaucoma patients from Iowa and to determine the expression pattern of genes in the locus in human eyes. Methods A cohort of 545 POAG patients and 297 control subjects from Iowa were genotyped with a single nucleotide polymorphism (SNP; rs4236601) in the chromosome 7q31 locus using a quantitative polymerase chain reaction (PCR) assay. The expression of genes within the 7q31 locus, caveolin-1 (CAV1) and caveolin-2 (CAV2) in human eyes was investigated with immunohistochemistry. Results The minor allele frequency (MAF) of rs4236601 was 27% in control subjects and 29% in POAG patients. We detected no statistical difference when we compared the allele frequencies of rs4236601 between POAG patients and control subjects (p=0.5). Similarly, we detected no statistical difference in the frequency of the three possible rs4236601 genotypes between patients and controls (p=0.22). Immunohistochemistry showed caveolin expression in human retina, ciliary muscle, trabecular meshwork, and Schlemm’s canal. In our small cohort of donor eyes, the genotype of rs4236601 did not obviously influence labeling intensity or distribution of CAV1 and CAV2 in the retina. Conclusions A genome-wide association study of subjects from Iceland mapped the first common genetic risk factor for POAG to a small region of the genome on chromosome 7q31 that contains the caveolin genes CAV1 and CAV2. We were unable to detect this association in our patients from Iowa, suggesting that this risk factor may not have a strong effect in all populations.