Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
Am J Ophthalmol. 2013 Feb;155(2):342-353.e5. doi: 10.1016/j.ajo.2012.07.023. Epub 2012 Oct 27.
To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients.
Retrospective observational case series.
We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results.
For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05).
Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG.
评估细胞周期蛋白依赖性激酶抑制剂 2B 反义非编码 RNA（CDKN2B-AS1）基因区域中单核苷酸多态性（SNP）与原发性开角型青光眼（POAG）患者青光眼特征之间的关联。
回顾性观察性病例系列。
我们研究了 10 个 CDKN2B-AS1 SNP 与来自 Glaucoma Genes and Environment（GLAUGEN）研究的 976 例 POAG 病例和来自 National Eye Institute Glaucoma Human Genetics Collaboration（NEIGHBOR）联盟的 1971 例病例之间的青光眼特征之间的关联。对于每个患者，我们选择了眼内较高值的特征。我们为青光眼特征创建了特定于队列的多变量模型，然后对结果进行了荟萃分析。
在与疾病风险降低相关的 10 个保护性 CDKN2B-AS1 SNP 中的 9 个（例如，rs2157719 中的 G 等位基因）中，携带这些较小等位基因的 POAG 患者的杯盘比更小（在诊断时每个 G 等位基因小 0.05 个单位；95%置信区间：-0.08，-0.03；P = 6.23E-05），尽管他们的眼内压（IOP）更高（在 DNA 采集时每个 G 等位基因高 0.70 毫米汞柱；95%置信区间：0.40，1.00；P = 5.45E-06）。对于与疾病风险增加相关的 1 个不利 rs3217992 SNP，携带 A 等位基因的 POAG 患者的杯盘比更大（在诊断时每个 A 等位基因大 0.05 个单位；95%置信区间：0.02，0.07；P = 4.74E-04），尽管他们的 IOP 更低（在 DNA 采集时每个 A 等位基因低 0.57 毫米汞柱；95%置信区间：-0.84，-0.29；P = 6.55E-05）。
影响 POAG 发病风险的 CDKN2B-AS1 SNP 等位基因也调节 POAG 患者视神经变性，突出了 CDKN2B-AS1 在 POAG 中的作用。
