Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population.
Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population.
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DOI：
10.1371/journal.pone.0054115
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fuse N
中科院分区：
文献类型：
--
作者：
Shi D;Funayama T;Mashima Y;Takano Y;Shimizu A;Yamamoto K;Mengkegale M;Miyazawa A;Yasuda N;Fukuchi T;Abe H;Ideta H;Nishida K;Nakazawa T;Richards JE;Fuse N
虽然家族研究和全基因组关联研究表明遗传因素在青光眼中起作用，但很难确定所涉及的特定遗传变异。我们检测了669个单核苷酸多态性（SNPs）与日本人群原发性开角型青光眼（POAG）和正常眼压性青光眼（NTG）的相关性，这些SNPs来自2号染色体区域，包括GLC 1B青光眼基因座。我们进行了两阶段的病例对照研究。第一组包括123例POAG患者，121例NTG患者和120名对照者;第二组包括187例POAG患者，286例NTG患者和271名对照者。在第一轮筛选中显示与POAG显著相关的6个SNP中，在第二轮中测试了7个SNP。HK 2基因编码序列中的Rs678350与POAG有显著的等位基因关联（第二阶段p=0.0027，荟萃分析 p = 2.7XE-4），与NTG有显著的等位基因关联（第二阶段p=4.7XE-4，荟萃分析p = 1.0XE-5）。 尽管TMEM 182基因中的等位基因在第二轮中没有显示出与青光眼的显著关联，但TMEM 182 rs 869833中具有A/A等位基因的受试者显示出更差的视野平均偏差（p = 0.01）。 尽管NCK 2基因编码序列中的rs 2033008在第一轮中未显示出显著关联，但其先前已显示出与NTG的关联，因此在第二轮中测试其与NTG的关联（在第二阶段中p=0.0053）。 免疫组化结果显示，HK 2和NCK 2均表达于视网膜神经节细胞层。一旦考虑到多重测试，在第二阶段，只有HK 2显示出与POAG和NTG的显著关联。我们的数据也支持以前的NCK 2与NTG相关的报道，并提出了关于TMEM 182在表型变异中可能发挥什么作用的问题。我们的数据表明，香港2可能发挥重要作用的NTG在日本人口。
Although family studies and genome-wide association studies have shown that genetic factors play a role in glaucoma, it has been difficult to identify the specific genetic variants involved. We tested 669 single nucleotide polymorphisms (SNPs) from the region of chromosome 2 that includes the GLC1B glaucoma locus for association with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese population. We performed a two-stage case-control study. The first cohort consisted of 123 POAG cases, 121 NTG cases and 120 controls: the second cohort consisted of 187 POAG cases, 286 NTG cases, and 271 controls. Out of six SNPs showing significant association with POAG in the first round screening, seven SNPs were tested in the second round. Rs678350 in the HK2 gene coding sequence showed significant allelic (p = 0.0027 in Stage Two, 2.7XE-4 in meta-analysis) association with POAG, and significant allelic (p = 4.7XE-4 in Stage Two, 1.0XE-5 in meta-analysis) association with NTG. Although alleles in the TMEM182 gene did not show significant association with glaucoma in the second round, subjects with the A/A allele in TMEM182 rs869833 showed worse visual field mean deviation (p = 0.01). Even though rs2033008 in the NCK2 gene coding sequence did not show significant association in the first round, it had previously shown association with NTG so it was tested for association with NTG in round 2 (p = 0.0053 in Stage Two). Immunohistochemistry showed that both HK2 and NCK2 are expressed in the retinal ganglion cell layer. Once multi-testing was taken into account, only HK2 showed significant association with POAG and NTG in Stage Two. Our data also support previous reports of NCK2 association with NTG, and raise questions about what role TMEM182 might play in phenotypic variability. Our data suggest that HK2 may play an important role in NTG in the Japanese population.
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影响因子：
4.1
作者：
HITCHINGS, RA;ANDERTON, SA
通讯作者：
ANDERTON, SA
影响因子：
7.7
作者：
ECHWALD, SM;BJORBAEK, C;PEDERSEN, O
通讯作者：
PEDERSEN, O
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8.2
作者：
LAAKSO, M;MALKKI, M;DEEB, SS
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DEEB, SS
影响因子：
3.5
作者：
Sarfarazi, M
通讯作者：
Sarfarazi, M
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3.5
作者：
Pasutto, Francesca;Keller, Kate E.;Wirtz, Mary K.
通讯作者：
Wirtz, Mary K.