Department of Ophthalmology, Shandong Shanxian Central Hospital, Heze, China.
Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1169-1176. doi: 10.26355/eurrev_202102_24819.
The aim of this study was to investigate the relationships of aquaporin 4 (AQP4) rs200498749, rs149465 and rs650217 polymorphisms and gene expression with diabetic retinopathy (DR).
A total of 400 patients with diabetes mellitus (DM) treated in our hospital were enrolled in this study. All subjects were divided into two groups, including DM group (n=200, without DR) and DR group (n=200, with DR). The polymorphisms rs200498749, rs149465 and rs650217 of AQP4 gene were analyzed in the two groups. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect gene expression, and statistical analysis was performed in combination with clinical data.
The distribution of alleles of AQP4 rs650217 (p=0.015) in DR group was different from that in DM group, and the frequency of T allele was significantly higher in DR group than DM group. The distribution of genotypes of AQP4 rs149465 (p=0.000) and rs650217 (p=0.000) showed statistically significant difference between DR group and DM group. The frequency of AA genotype of polymorphism rs149465 and CT genotype of polymorphism rs650217 was significantly higher in DR group than DM group. Besides, there was a difference in the distribution of recessive models of AQP4 rs149465 (p=0.023) and rs650217 (p=0.014) between DR group and DM group. DR group exhibited remarkably lowered frequency of AA + AT recessive model of the polymorphism rs149465 and raised frequency of CT + TT recessive model of the polymorphism rs650217. Similarly, a difference was found in the distribution of haplotypes CAT (p=0.014) and CTC (p=0.003) of AQP4 rs200498749, rs149465 and rs650217 between DR group and DM group. The polymorphism rs200498749 of AQP4 gene was significantly correlated with AQP4 gene expression (p<0.05). Meanwhile, the expression of AQP4 gene was clearly higher in patients with CC genotype in DR group (p<0.05). AQP4 polymorphism rs200498749 was related to fasting blood glucose (p=0.000) and hemoglobin A1c (HbA1c) (p=0.000) in DR group, and polymorphism rs650217 had an association with serum creatinine level (p=0.034). AQP4 polymorphisms rs149465 (p=0.023) and rs650217 (p=0.042) were correlated with clinical stage in DR group. In addition, the proportion of patients with AA genotype of rs149465 at stage VI and with TT genotype of rs650217 at stage I rose significantly (p<0.05).
AQP4 gene polymorphism has a potential relationship with the susceptibility and progression of DR.
本研究旨在探讨水通道蛋白 4（AQP4）rs200498749、rs149465 和 rs650217 多态性与基因表达与糖尿病视网膜病变（DR）的关系。
选取我院收治的 400 例糖尿病患者纳入本研究。所有患者分为两组，DM 组（n=200，无 DR）和 DR 组（n=200，有 DR）。分析 AQP4 基因多态性 rs200498749、rs149465 和 rs650217。采用实时定量聚合酶链反应（RT-qPCR）检测基因表达，并结合临床资料进行统计分析。
DR 组 AQP4 rs650217 等位基因的分布（p=0.015）与 DM 组不同，DR 组 T 等位基因的频率明显高于 DM 组。DR 组 AQP4 rs149465（p=0.000）和 rs650217（p=0.000）的基因型分布存在统计学差异。DR 组 AQP4 rs149465 多态性 AA 基因型和 rs650217 多态性 CT 基因型的频率明显高于 DM 组。此外，DR 组和 DM 组 AQP4 rs149465（p=0.023）和 rs650217（p=0.014）的隐性模型分布存在差异。DR 组 AQP4 rs149465 多态性 AA+AT 隐性模型频率明显降低，rs650217 多态性 CT+TT 隐性模型频率升高。同样，DR 组和 DM 组 AQP4 rs200498749、rs149465 和 rs650217 的 CAT（p=0.014）和 CTC（p=0.003）单倍型分布存在差异。AQP4 基因的 rs200498749 多态性与 AQP4 基因表达显著相关（p<0.05）。同时，DR 组中 CC 基因型患者的 AQP4 基因表达明显升高（p<0.05）。AQP4 多态性 rs200498749 与 DR 组的空腹血糖（p=0.000）和糖化血红蛋白（HbA1c）（p=0.000）相关，rs650217 与血清肌酐水平（p=0.034）相关。DR 组的 AQP4 rs149465（p=0.023）和 rs650217（p=0.042）多态性与临床分期相关。此外，DR 组 VI 期 AA 基因型和 I 期 TT 基因型患者的比例明显升高（p<0.05）。
AQP4 基因多态性与 DR 的易感性和进展有关。
