...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Medical Genomics >Genetic association between CDKN2B/CDKN2B-AS1 gene polymorphisms with primary glaucoma in a North Indian cohort: an original study and an updated meta-analysis
【24h】

Genetic association between CDKN2B/CDKN2B-AS1 gene polymorphisms with primary glaucoma in a North Indian cohort: an original study and an updated meta-analysis

机译：CDKN2B / CDKN2B-AS1基因多态性与北印度群岛原发性青光眼之间的遗传关联：原始研究和更新的META分析

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Variants in CDKN2B/CDKN2B-AS1 have been reported to modulate glaucoma risk in several GWAS across different populations. CDKN2B/CDKN2A encodes tumor suppressor proteins p16INK4A/p15INK4B which influences cell proliferation/senescence in RGCs, the degeneration of which is a risk factor for glaucoma. CDKN2B-AS1 codes a long non-coding RNA in antisense direction and is involved in influencing nearby CDKN2A/CDKN2B via regulatory mechanisms. Current study investigated four SNPs (rs2157719, rs3217992, rs4977756, rs1063192) of aforementioned genes in a case–control study in a North Indian cohort. Genotyping was done with Taqman chemistry. In addition, an updated meta-analysis was performed. Two SNPs, rs3217992 and rs2157719 were found to be significantly associated with the disease. The frequency of ‘T’ allele of rs3217992 was significantly lower in cases (POAG/PACG) [p?=?0.045; OR?=?0.80(CI?=?0.65–0.99) and p?=?0.024; OR?=?0.73(CI?=?0.55–0.96)], respectively than in controls. Genetic model analysis revealed that TT? ?CT genotype confers 0.73-fold protection against POAG [p?=?0.047; OR?=?0.73(CI?=?0.54–0.99)] and trend assumed additive model gives 0.53 times higher protection against PACG progression. However the association of rs3217992 with POAG and PACG did not remain significant after Bonferroni correction. For rs2157719, the ‘C’ allele was found to be less prevalent among cases (POAG/PACG) with respect to controls. Cochran Armitage trend test assuming additive model revealed 0.77 and 0.64-fold protection against POAG and PACG respectively. Bonferroni correction (pcorr?=?0.003) was applied and the association of rs2157719 remained significant in PACG cases but not among POAG cases (p?=?0.024). The ‘CC’ genotype also confers protection against primary glaucoma (POAG/PACG) among males and female subjects. The frequency rs1063192 and rs4977756 did not vary significantly among subjects, however the haplotype ‘CATA’ was found to be associated with increased glaucoma risk. An updated meta-analysis conducted on pooled studies on POAG cases and controls revealed significant association between rs1063192, rs2157719, rs4977756 and POAG except rs3217992. The study concludes significant association between INK4 variants and primary glaucoma in the targeted North Indian?Punjabi cohort. We believe that deep-sequencing of INK4 locus may help in identifying novel variants modifying susceptibility to glaucoma. Functional studies can further delineate the role of CDKN2B and CDKN2B-AS1 in primary glaucoma for therapeutic intervention.
机译：据报道，CDKN2B / CDKN2B-AS1中的变体在不同群体中调节几个GWA的青光眼风险。 CDKN2B / CDKN2A编码肿瘤抑制蛋白p16ink4a / p15ink4b，其影响RGCs中细胞增殖/衰老，其变性是青光眼的危险因素。 CDKN2B-AS1根据反义方向编码长的非编码RNA，并参与通过调节机制影响附近的CDKN2A / CDKN2B。目前的研究在北印度队列的病例对照研究中调查了上述基因的四种SNP（RS2157719，RS497756，RS1063192）。基因分型用塔克曼化学完成。此外，还进行了更新的元分析。发现两个SNP，RS3217992和RS2157719与疾病显着相关。病例（POAG / PACG）[P吗？= 0.045;或者？=？0.80（CI？= 0.65-0.99）和P？= 0.024;或？=？= 0.73（CI？= 0.55-0.96）]，分别不是对照。遗传模型分析显示TT？ ？CT基因型赋予对POAG的0.73倍的保护[P？= 0.047;或者？=？0.73（CI？= 0.54-0.99）]和趋势假定的添加剂模型，对PACG进展的保护较高的0.53倍。然而，在Bonferroni校正后，RS3217992与POAG和PACG的关联并未保持显着。对于RS2157719，发现“C”等位基因在对照方面的情况下不太普遍（POAG / PACG）。 Cochran Armitage趋势试验假设添加剂模型分别揭示了0.77％和0.64倍的POG和PACG。施用Bonferroni校正（Pcorr？= 0.003），RS2157719的关联在PACG病例中仍然显着，但不是POG病例（P？= 0.024）。 “CC”基因型还赋予了男性和女性受试者的原发性青光眼（POAG / PACG）的保护。频率RS1063192和RS4977756在受试者之间没有显着变化，但是发现单倍型'CACA'与增加的青光眼风险相关。关于Poag案例和控制的汇总研究进行了更新的荟萃分析，并在RS1063192，RS2157719，RS4977756和RS3217992之外进行了重大关联。该研究总结了Ink4变体与北印度印度的初级青光眼之间的重大关联？Punjabi Cohort。我们认为Ink4基因座的深度测序可能有助于识别改性对青光眼的易感性的新型变体。功能性研究可以进一步描绘CDKN2B和CDKN2B-AS1在原发性青光眼中的作用进行治疗干预。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号