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低血清脑源性神经营养因子而非脑源性神经营养因子基因Val66Met多态性与中国2型糖尿病患者的糖尿病视网膜病变相关。

LOW SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR BUT NOT BRAIN-DERIVED NEUROTROPHIC FACTOR GENE VAL66MET POLYMORPHISM IS ASSOCIATED WITH DIABETIC RETINOPATHY IN CHINESE TYPE 2 DIABETIC PATIENTS.

作者信息

Guo Min, Liu Huan, Li Shan-Shan, Jiang Fu-Li, Xu Jin-Mei, Tang Ying-Ying

机构信息

*Department of Endocrinology and Metabolic Disease, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China; †College of Pharmacy, Harbin Medical University, Harbin, China; and ‡Cardiovascular Department, The Fifth Hospital of Heilongjiang Province, Harbin, China.

出版信息

Retina. 2017 Feb;37(2):350-358. doi: 10.1097/IAE.0000000000001132.

Abstract

BACKGROUND/PURPOSE: The aim of our research was to investigate the potential role of brain-derived neurotrophic factor (BDNF) in diabetic retinopathy (DR). Measurement of serum circulating levels of BDNF and analysis of polymorphism of BDNF gene (Val66Met) were applied and compared with diabetic patients without DR.

METHODS

From February 2014 and March 2015, all eligible patients with Type 2 diabetic mellitus at our hospital were consecutively recruited (N = 404). Their serum BDNF levels were detected by enzyme-linked immunosorbent assay. BDNF val66met polymorphism genotyping was conducted according to the laboratory's standard protocol. At baseline, demographic and clinical data were taken. The relationship of BDNF with DR was investigated with the use of logistic regression models. Receiver operating characteristic curves were used to test the overall accuracy of BDNF and other markers.

RESULTS

Diabetic patients with DR and vision-threatening DR had significantly lower BDNF levels on admission (P < 0.0001 both). The BDNF genotyping results showed that there was no difference between the diabetic patients with DR and those without DR. Multivariate logistic regression analysis adjusted for common risk factors showed that serum BDNF levels were independent risk factors for DR (odds ratio = 0.86; 95% confidence interval [CI]: 0.80-0.92; P < 0.0001) and vision-threatening DR (odds ratio = 0.79; 95% CI: 0.75-0.85; P < 0.0001). Brain-derived neurotrophic factor improved the area under the receiver operating characteristic curve of the diabetes duration for DR from 0.69 (95% CI: 0.60-0.76) to 0.85 (95% CI: 0.79-0.90; P < 0.01) and for vision-threatening DR from 0.77 (95% CI: 0.67-0.87) to 0.86 (95% CI: 0.80-0.92; P < 0.01).

CONCLUSION

The present study demonstrated that, rather than Val66Met polymorphism, decreased serum levels of BDNF were associated with DR and vision-threatening DR in Chinese Type 2 diabetic patients, suggesting a possible role of BDNF in the pathogenesis of DR complications.

摘要

背景/目的:我们研究的目的是探讨脑源性神经营养因子(BDNF)在糖尿病视网膜病变(DR)中的潜在作用。检测血清中BDNF的循环水平,并分析BDNF基因(Val66Met)的多态性,同时与无DR的糖尿病患者进行比较。

方法

2014年2月至2015年3月,我院连续招募了所有符合条件的2型糖尿病患者(N = 404)。采用酶联免疫吸附测定法检测他们的血清BDNF水平。根据实验室标准方案进行BDNF val66met多态性基因分型。在基线时,收集人口统计学和临床数据。使用逻辑回归模型研究BDNF与DR的关系。采用受试者工作特征曲线来检验BDNF和其他标志物的总体准确性。

结果

患有DR和威胁视力的DR的糖尿病患者入院时BDNF水平显著降低(两者P < 0.0001)。BDNF基因分型结果显示,患有DR的糖尿病患者与未患DR的糖尿病患者之间没有差异。对常见危险因素进行校正的多变量逻辑回归分析表明,血清BDNF水平是DR(比值比 = 0.86;95%置信区间[CI]:0.80 - 0.92;P < 0.0001)和威胁视力的DR(比值比 = 0.79;95% CI:0.75 - 0.85;P < 0.0001)的独立危险因素。脑源性神经营养因子使糖尿病病程对DR的受试者工作特征曲线下面积从0.69(95% CI:0.60 - 0.76)提高到0.85(95% CI:0.79 - 0.90;P < 0.01),对威胁视力的DR从0.77(95% CI:0.67 - 0.87)提高到0.86(95% CI:0.80 - 0.92;P < 0.01)。

结论

本研究表明,在中国2型糖尿病患者中,与DR和威胁视力的DR相关的是血清BDNF水平降低,而非Val66Met多态性,这表明BDNF在DR并发症的发病机制中可能发挥作用。

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