title: The interaction of combined effects of the BDNF and PRKCG genes and negative life events in major depressive disorder.
abstract: Major depressive disorder (MDD) is a mental disorder that results from complex interplay between multiple and partially overlapping sets of susceptibility genes and environmental factors. The brain derived neurotrophic factor (BDNF) and Protein kinase C gamma type (PRKCG) are logical candidate genes in MDD. Among diverse environmental factors, negative life events have been suggested to exert a crucial impact on brain development. In the present study, we hypothesized that interactions between genetic variants in BDNF and PRKCG and negative life events may play an important role in the development of MDD. We recruited a total of 406 patients with MDD and 391 age- and gender-matched control subjects. Gene-environment interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). Under a dominant model, we observed a significant three-way interaction among BDNF rs6265, PRKCG rs3745406, and negative life events. The gene-environment combination of PRKCG rs3745406 C allele, BDNF rs6265 G allele and high level of negative life events (C-G-HN) was significantly associated with MDD (OR, 5.97; 95% CI, 2.71-13.15). To our knowledge, this is the first report of evidence that the BDNF-PRKCG interaction may modify the relationship between negative life events and MDD in the Chinese population.
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, People's Republic of China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, People's Republic of China.
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, People's Republic of China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan 030001, People's Republic of China. Electronic address: krzhang_sxmu@vip.163.com.
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics* / Q000523:psychology*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000235:genetics*; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; C087857:protein kinase C gamma; D011493:Protein Kinase C
keywords: Brain derived neurotrophic factor (BDNF); Gene–environment interaction; Major depressive disorder (MDD); Negative life events; Protein kinase C gamma type (PRKCG)