A Genome-Wide Scan for MicroRNA-Related Genetic Variants Associated With Primary Open-Angle Glaucoma.
A Genome-Wide Scan for MicroRNA-Related Genetic Variants Associated With Primary Open-Angle Glaucoma.
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DOI：
10.1167/iovs.17-22410
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发表时间：
2017-10-01
影响因子：
4.4
通讯作者：
International Glaucoma Genetics Consortium (IGGC)
中科院分区：
文献类型：
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作者：
Ghanbari M;Iglesias AI;Springelkamp H;van Duijn CM;Ikram MA;Dehghan A;Erkeland SJ;Klaver CCW;Meester-Smoor MA;International Glaucoma Genetics Consortium (IGGC)
利用遗传学数据鉴定与原发性开角型青光眼（POAG）相关的microRNAs（miRNAs）。miRNAs是一类转录后调节基因表达的小分子非编码RNA。基因3′非翻译区（3′ UTR）内的miRNA或miRNA结合位点的遗传变异预计会影响miRNA功能并导致疾病风险。最近的全基因组关联研究的数据，眼内压，垂直杯盘比（VCDR），cupa面积和盘面积被用来调查与POAG内表型的关联的miRNA。根据它们与POAG的关联研究了相关miRNA的推定靶标，并通过转染实验在细胞系中测试了miRNA的调节。在411种miRNA变体中，pre-miR-612末端环中的rs 12803915：A/G和miR-4707种子序列中的rs 2273626：A/C与VCDR和杯面积显著相关（P值< 1.2 × 10−4）。第一个变体被证明增加miR-612表达。我们发现第二种变体不影响miR-4707的生物发生，但减少了miR-4707- 3 p与CARD 10的结合，CARD 10是一种已知参与青光眼的基因。此外，在72，052个miRNA结合位点变异体中，47个与四种POAG内表型显著相关（P值< 6.9 × 10−6）。其中，我们强调了10种更可能影响POAG中miRNA介导的基因调控的变体。这些包括rs3217992和rs 1063192，实验表明它们影响miR-138- 3 p和miR-323 b-5 p介导的CDKN 2B调节。我们鉴定了许多与POAG内表型相关的miRNA。所鉴定的miRNAs及其靶基因是未来POAG miRNAs相关治疗研究的候选基因。
To identify microRNAs (miRNAs) involved in primary open-angle glaucoma (POAG), using genetic data. MiRNAs are small noncoding RNAs that posttranscriptionally regulate gene expression. Genetic variants in miRNAs or miRNA-binding sites within gene 3′-untranslated regions (3′UTRs) are expected to affect miRNA function and contribute to disease risk. Data from the recent genome-wide association studies on intraocular pressure, vertical cup-to-disc ratio (VCDR), cupa area and disc area were used to investigate the association of miRNAs with POAG endophenotypes. Putative targets of the associated miRNAs were studied according to their association with POAG and tested in cell line by transfection experiments for regulation by the miRNAs. Of 411 miRNA variants, rs12803915:A/G in the terminal loop of pre–miR-612 and rs2273626:A/C in the seed sequence of miR-4707 were significantly associated with VCDR and cup area (P values < 1.2 × 10−4). The first variant is demonstrated to increase the miR-612 expression. We showed that the second variant does not affect the miR-4707 biogenesis, but reduces the binding of miR-4707-3p to CARD10, a gene known to be involved in glaucoma. Moreover, of 72,052 miRNA-binding-site variants, 47 were significantly associated with four POAG endophenotypes (P value < 6.9 × 10−6). Of these, we highlighted 10 variants that are more likely to affect miRNA-mediated gene regulation in POAG. These include rs3217992 and rs1063192, which have been shown experimentally to affect miR-138-3p– and miR-323b-5p–mediated regulation of CDKN2B. We identified a number of miRNAs that are associated with POAG endophenotypes. The identified miRNAs and their target genes are candidates for future studies on miRNA-related therapies for POAG.
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影响因子：
14.9
作者：
Karali M;Persico M;Mutarelli M;Carissimo A;Pizzo M;Singh Marwah V;Ambrosio C;Pinelli M;Carrella D;Ferrari S;Ponzin D;Nigro V;di Bernardo D;Banfi S
通讯作者：
Banfi S
影响因子：
3.7
作者：
Cammaerts S;Strazisar M;De Rijk P;Del Favero J
通讯作者：
Del Favero J
影响因子：
3.7
作者：
Kim HK;Prokunina-Olsson L;Chanock SJ
通讯作者：
Chanock SJ
影响因子：
--
作者：
Ghanbari, Mohsen;Franco, Oscar H.;Dehghan, Abbas
通讯作者：
Dehghan, Abbas
影响因子：
4.1
作者：
Foster, PJ;Buhrmann, R;Johnson, GJ
通讯作者：
Johnson, GJ