title: Functional Val66Met polymorphism of Brain-derived neurotrophic factor in type 2 diabetes with depression in Han Chinese subjects.
abstract: 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.
authors: 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. xfx22081@vip.163.com.
authors: Jian-Xin
authors: JX
authors: Zhou
authors: He-Chao
authors: HC
authors: Li
authors: Xue-Jun
authors: XJ
authors: Bai
authors: Bao-Cheng
authors: BC
authors: Chang
authors: Chun-Jun
authors: CJ
authors: Li
authors: Pei
authors: P
authors: Sun
authors: Li-Ming
authors: LM
authors: Chen
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics*; D002681:China; D003866:Depressive Disorder / Q000097:blood / Q000150:complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D019208:Brain-Derived Neurotrophic Factor
references: Diabetes Care. 2000 Jul;23(7):934-42
references: 10895843
references: Biol Psychiatry. 2005 Aug 15;58(4):307-14
references: 16005437
references: Brain Behav. 2011 Nov;1(2):119-24
references: 22399091
references: EMBO J. 2000 Mar 15;19(6):1290-300
references: 10716929
references: J Neurosci. 2007 Oct 31;27(44):11851-5
references: 17978023
references: Neuromolecular Med. 2004;5(1):11-25
references: 15001809
references: Neuropsychopharmacology. 2005 Jul;30(7):1353-61
references: 15770238
references: Mol Psychiatry. 2010 Mar;15(3):260-71
references: 18852698
references: J Psychosom Res. 2007 Jan;62(1):31-8
references: 17188118
references: Neuroreport. 2007 Aug 6;18(12):1291-3
references: 17632285
references: J Affect Disord. 2010 Mar;121(3):212-9
references: 19539999
references: Diabetes Care. 2005 Jun;28(6):1339-45
references: 15920049
references: PLoS One. 2012;7(9):e44569
references: 22973461
references: Brain Behav. 2012 Nov;2(6):726-31
references: 23170235
references: Nat Rev Neurosci. 2006 Jun;7(6):477-84
references: 16688123
references: CNS Spectr. 2002 Feb;7(2):140-2, 144-7
references: 15220856
references: Med Hypotheses. 2008;70(2):424-9
references: 17553627
references: PLoS One. 2012;7(8):e42785
references: 22880108
references: Psychiatry Res. 2002 Mar 15;109(2):143-8
references: 11927139
references: Diabetologia. 2007 Feb;50(2):431-8
references: 17151862
references: Biol Psychiatry. 2008 Sep 15;64(6):527-32
references: 18571629
references: Diabetes Care. 2001 Jun;24(6):1069-78
references: 11375373
references: BMC Med Res Methodol. 2011 May 20;11:74
references: 21595982
references: Science. 2006 Oct 6;314(5796):140-3
references: 17023662
references: Diabetes Care. 2007 Dec;30(12):3005-10
references: 17717284
references: J Gen Intern Med. 2006 Jun;21(6):547-52
references: 16808734
references: Prim Care Companion J Clin Psychiatry. 2004;6(4):152-158
references: 15361918
references: Trends Neurosci. 2004 Oct;27(10):589-94
references: 15374669
references: JAMA. 1996 Jul 24-31;276(4):293-9
references: 8656541
references: J Neurosci. 2005 Jun 29;25(26):6156-66
references: 15987945
references: Diabetes Care. 2007 Sep;30(9):2222-7
references: 17536067
references: Transl Psychiatry. 2012 Jan 31;2:e74
references: 22832736
references: Clin Biochem. 2008 Jul;41(10-11):812-7
references: 18402781
references: Psychosom Med. 2007 May;69(4):300-5
references: 17470664
references: Brain Behav. 2012 Nov;2(6):778-88
references: 23170240
references: Neurobiol Aging. 2006 Dec;27(12):1834-7
references: 16343697
references: Neurogastroenterol Motil. 2013 Feb;25(2):162-e85
references: 23020799
references: Int J Geriatr Psychiatry. 2004 Jul;19(7):634-40
references: 15254919
references: Mol Psychiatry. 2002;7(2):136-7
references: 11840305
references: Diabet Med. 2006 Nov;23(11):1165-73
references: 17054590
references: Psychiatry Investig. 2010 Dec;7(4):236-42
references: 21253406
references: East Mediterr Health J. 2001 May;7(3):481-91
references: 12690770
references: Brain Cogn. 2009 Nov;71(2):147-52
references: 19481324
references: Cell. 2003 Jan 24;112(2):257-69
references: 12553913
references: J Clin Nurs. 2013 Jan;22(1-2):80-8
references: 23134147
references: Neuropsychobiology. 2003;48(4):186-9
references: 14673216