HDAC9 rs11984041 polymorphism is associated with diabetic retinopathy in Slovenian patients with type 2 diabetes mellitus.

ABSTRACT

AIM: 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). METHODS: 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. RESULTS: 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/mm2 vs. 12 ± 6/mm2, respectively). CONCLUSIONS: 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.