一种调控miR-126的基因变异与威胁视力的糖尿病视网膜病变相关。
A genetic variant regulating miR-126 is associated with sight threatening diabetic retinopathy.
作者信息
McAuley Annie K, Dirani Mohamed, Wang Jie Jin, Connell Paul P, Lamoureux Ecosse L, Hewitt Alex W
机构信息
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Westmead, NSW, Australia.
出版信息
Diab Vasc Dis Res. 2015 Mar;12(2):133-8. doi: 10.1177/1479164114560160. Epub 2015 Jan 23.
BACKGROUND
The regulation of miR-126 by rs4636297 single nucleotide polymorphism (SNP) has been implicated in the pathogenesis of neovascularisation by promoting vascular endothelial growth factor, suggesting it could be associated with sight threatening diabetic retinopathy (STDR), but has not been previously investigated or reported.
MATERIALS AND METHODS
A case control study of 531 individuals with diabetes was genotyped for the rs4636297 SNP, using the Sequenom iPLEX Gold chemistry. STDR included people with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). Association was tested using logistic regression analysis, adjusting for confounding variables.
RESULTS
In an additive model, the A allele of rs4636297 SNP is significantly associated with STDR compared to people with none or mild diabetic retinopathy (DR) (odds ratio (OR) = 2.02, 95% confidence interval (CI) = 1.22-3.35, p = 0.006).
CONCLUSION
The A allele of rs4636297, known to be the non-functional allele for post-translational regulation of miR-126, is associated with STDR. This finding suggests that this locus would be a potential therapeutic target for inhibiting the development of DR.
背景
rs4636297单核苷酸多态性（SNP）对miR-126的调控通过促进血管内皮生长因子参与了新生血管形成的发病机制，提示其可能与威胁视力的糖尿病视网膜病变（STDR）相关，但此前尚未进行研究或报道。
材料与方法
采用Sequenom iPLEX Gold技术对531例糖尿病患者进行rs4636297 SNP基因分型，开展病例对照研究。STDR包括重度非增殖性糖尿病视网膜病变（NPDR）或增殖性糖尿病视网膜病变（PDR）患者。采用逻辑回归分析检验关联性，并对混杂变量进行校正。
结果
在加性模型中，与无糖尿病视网膜病变（DR）或轻度DR患者相比，rs4636297 SNP的A等位基因与STDR显著相关（优势比（OR）= 2.02，95%置信区间（CI）= 1.22 - 3.35，p = 0.006）。
结论
已知rs4636297的A等位基因为miR-126翻译后调控的无功能等位基因，其与STDR相关。这一发现表明该基因座可能是抑制DR发展的潜在治疗靶点。
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