汉族 2 型糖尿病伴发抑郁患者脑源性神经营养因子 Val66Met 功能性多态性。
Functional Val66Met polymorphism of Brain-derived neurotrophic factor in type 2 diabetes with depression in Han Chinese subjects.
机构信息
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
出版信息
Behav Brain Funct. 2013 Aug 22;9:34. doi: 10.1186/1744-9081-9-34.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depression. Individuals with type 2 diabetes (T2DM) have a high prevalence of major depression and low levels of BDNF. We therefore explored whether the BDNF Val66Met polymorphism is associated with co-morbid depression and whether depression affects the serum levels of BDNF in a Han Chinese subjects with T2DM.
METHODS
A Total of 296 T2DM patients and 70 healthy volunteers (Health control, HC group) were recruited in this study. T2DM patients were divided into two subgroups: depressive diabetes group (DDM group, n = 64) and non-depressive diabetes group (NDDM group, n = 232), according to the presence or the absence of depression assessed by Center for Epidemiologic Studies Depression Scale (CES-D) and Patient Health Questionnaire-9 (PHQ-9). Val66Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Serum BDNF levels were measured by ELISA kit.
RESULTS
In this study, 21.6% (64/296) patients with T2DM had depression. The BDNF Val66Met genotype distributions were statistically different among the three groups (χ2 = 7.39, p < 0.05). DDM group carried the highest frequencies of Met allele (53.9%) compared to HC group (39.3%) and NDDM group (38.8%). Subjects with Met/Met had lowest serum BDNF levels (76.59 ± 5.12 pg/ml, F = 7.39, p < 0.05) compared to subjects with Val/Met (79.04 ± 5.19 pg/ml) and Val/Val (83.83 ± 3.97 pg/ml). Within T2DM group, it was also observed that the serum BDNF levels in DDM group were significantly lower than those in NDDM group (76.67 ± 5.35 vs. 79.84 ± 3.97 pg/ml, p < 0.05). In type 2 diabetes subjects, BDNF serum levels were significant correlations with genotypes (r = -0.346, p < 0.01), depression scores (r = -0.486, p < 0.01) and HbA1c (r = -0.168, p < 0.05). After adjustment for gender, HbA1c, BMI and numbers of complications, BDNF Val/Met genotype distributions (OR = 2.105, p < 0.05) and decreased serum BDNF levels (OR = 0.835, p < 0.01) were independently associated with depression in T2DM.
CONCLUSIONS
The BDNF Val66Met polymorphism might be implicated in the pathogenesis of depression in T2DM by decreasing serum BDNF levels in Han Chinese Subjects.
背景
脑源性神经营养因子（BDNF）与重度抑郁症的发病机制有关。2 型糖尿病（T2DM）患者重度抑郁症的患病率较高，BDNF 水平较低。因此，我们探讨了 BDNF Val66Met 多态性是否与合并抑郁症有关，以及抑郁症是否会影响汉族 T2DM 患者的血清 BDNF 水平。
方法
本研究共招募了 296 例 T2DM 患者和 70 名健康志愿者（健康对照组，HC 组）。根据中心流行病学研究抑郁量表（CES-D）和患者健康问卷-9（PHQ-9）评估的抑郁情况，将 T2DM 患者分为抑郁性糖尿病组（DDM 组，n=64）和非抑郁性糖尿病组（NDDM 组，n=232）。采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测 Val66Met 多态性。采用 ELISA 试剂盒检测血清 BDNF 水平。
结果
本研究中，296 例 T2DM 患者中 21.6%（64/296）患有抑郁症。三组间 BDNF Val66Met 基因型分布差异有统计学意义（χ2=7.39，p<0.05）。DDM 组的 Met 等位基因频率（53.9%）明显高于 HC 组（39.3%）和 NDDM 组（38.8%）。Met/Met 基因型患者的血清 BDNF 水平最低（76.59±5.12pg/ml，F=7.39，p<0.05），低于 Val/Met（79.04±5.19pg/ml）和 Val/Val（83.83±3.97pg/ml）基因型患者。在 T2DM 组中，也观察到 DDM 组的血清 BDNF 水平明显低于 NDDM 组（76.67±5.35 vs. 79.84±3.97pg/ml，p<0.05）。在 2 型糖尿病患者中，BDNF 血清水平与基因型（r=-0.346，p<0.01）、抑郁评分（r=-0.486，p<0.01）和 HbA1c（r=-0.168，p<0.05）显著相关。在校正性别、HbA1c、BMI 和并发症数量后，BDNF Val/Met 基因型分布（OR=2.105，p<0.05）和血清 BDNF 水平降低（OR=0.835，p<0.01）与 T2DM 患者的抑郁独立相关。
结论
BDNF Val66Met 多态性可能通过降低汉族 2 型糖尿病患者的血清 BDNF 水平，参与 2 型糖尿病患者抑郁症的发病机制。
Zotero 插件