Gene. 2021 Sep 5;796-797:145802. doi: 10.1016/j.gene.2021.145802. Epub 2021 Jun 24.
Histone deacetylase 9 (HDAC9) is an important regulator of transcription that has also been investigated as a candidate gene in some pathologies. Our aim was to investigate the association between rs2107595 and rs11984041 HDAC9 gene polymorphisms and diabetic retinopathy (DR) in Slovenian patients with type 2 diabetes mellitus (T2DM). We also investigated HDAC9 expression in the fibrovascular membranes (FVMs) of patients with proliferative DR (PDR).
Our study involved 1290 unrelated Slovenian patients with T2DM: 542 of them with DR as the study group, and 748 without DR as the control group. The investigated polymorphisms were genotyped using KASPar genotyping assay. The expression of HDAC9 was examined by immunohistochemistry in human FVM from 25 patients with PDR.
The T allele and TT genotype frequencies of the rs11984041 polymorphism were significantly higher in the study group compared to the controls. The logistic regression analysis showed that the carriers of the TT genotype of this polymorphism have a 3.76-fold increase (95% CI 1.04-11.67) in the risk of developing DR. The T allele of rs11984041 was associated with increased HDAC9 expression in FVMs, obtained from T2DM patients with PDR. Patients with the T allele of rs11984041 compared to the homozygotes for the wild type C allele exhibited higher density of HDAC9-positive cells (35 ± 10/mm vs. 12 ± 6/mm, respectively).
We observed a notable association between the TT genotype of rs11984041 and DR, indicating its possible role as a genetic risk factor for the development of this diabetic complication.
组蛋白去乙酰化酶 9（HDAC9）是转录的重要调节因子，也被作为某些病理的候选基因进行研究。我们的目的是研究斯洛文尼亚 2 型糖尿病患者中 HDAC9 基因 rs2107595 和 rs11984041 多态性与糖尿病视网膜病变（DR）之间的关系。我们还研究了增殖性糖尿病视网膜病变（PDR）患者纤维血管膜（FVM）中 HDAC9 的表达。
我们的研究涉及 1290 名无血缘关系的斯洛文尼亚 2 型糖尿病患者：542 名患有 DR 的患者为研究组，748 名无 DR 的患者为对照组。使用 KASPar 基因分型检测法对所研究的多态性进行基因分型。通过免疫组织化学法在 25 名 PDR 患者的人 FVM 中检测 HDAC9 的表达。
与对照组相比，rs11984041 多态性的 T 等位基因和 TT 基因型频率在研究组中显著更高。逻辑回归分析表明，该多态性 TT 基因型的携带者发生 DR 的风险增加 3.76 倍（95%CI 1.04-11.67）。rs11984041 的 T 等位基因与来自 PDR 的 2 型糖尿病患者的 FVM 中 HDAC9 表达增加相关。与野生型 C 等位基因纯合子相比，携带 rs11984041 的 T 等位基因的患者具有更高密度的 HDAC9 阳性细胞（分别为 35±10/mm 和 12±6/mm）。
我们观察到 rs11984041 的 TT 基因型与 DR 之间存在显著关联，表明其可能是这种糖尿病并发症发展的遗传风险因素。
