The rs6265 Polymorphism of the BDNF Gene Is Related to Higher-Lethality Suicide Attempts in the Korean Population

Abstract

Suicide is one of the most serious health and social problems and is a worldwide phenomenon. According to statistics from 2017, the suicide rate in South Korea was 24.3 per 100,000 individuals. 1 Although South Korea is a country with a declining suicide rate, its rate is still one of the highest among the Organization for Economic Cooperation and Development countries. Since the most important prevention is the early detection of groups at high risk for suicide, many studies and efforts to find high-risk groups have been steadily carried out, and many ge- Print ISSN 1738-3684 / On-line ISSN 1976 OPEN ACCESS netic studies have been conducted to identify candidate genes for suicidal behavior. Many studies on genetic associations have suggested that several genes, such as those encoding serotonin receptors and transporters, tryptophan hydroxylase, and brainderived neurotrophic factors (BDNFs), are related to suicidal behavior; however, these findings have not been consistently replicated. 2 BDNF is a neurotrophic factor involved in the development and maintenance of neural cells 3 and is important for cell survival and apoptosis in neural cells. 4 Substantial evidence has shown that the BDNF gene has a connection with the genetic etiology of psychiatric disorders and suicidal behavior. 5 Postmortem studies have shown reduced BDNF expression in suicide victims, 6 and major depressive disorder patients who attempted suicide have shown decreased plasma levels of BDNF. 7 BDNF is encoded by the BDNF gene located on chromosome 11, 8 and most genetic association studies between this gene and suicidal behavior were performed for the rs6265 polymorphism, which is also known as the Val66Met or G196A poly-Objective Since the risk of suicide cannot be predicted by clinical symptoms alone, and suicide is known to have a genetic component, the discovery of genetic markers that can predict the lethality of suicide attempts is a clinically important topic. There have been many studies aiming to determine whether the rs6265 polymorphism of the BDNF gene is associated with suicidality; however, the results have been mixed, and there have been few studies investigating the relationship between this polymorphism and suicide attempt lethality. Methods We assessed suicide lethality in 258 individuals who had attempted suicide using the relative risk ratio (RRR) scale and by genotyping the rs6265 polymorphism of the BDNF gene. Results The RRR score for suicide attempts was higher in subjects with Met/Val and Val/Val genotypes than in that with a Met/Met genotype (p=0.015). The RRR score for suicide attempts was also higher in Val allele carriers (Met/Val+Val/Val) than in Met/Met homozygotes (p=0.006). Conclusion This study demonstrates the possibility that the rs6265 polymorphism of the BDNF gene could be used as a genetic marker to predict the lethality of suicide attempts, but more replication studies are needed for the application of this result in clinical practice. Psychiatry Investig 2020;17(5):417-423cc This is an Open Access arti...

Risk and Protective Factors for Childhood Physical Abuse and Suicidal Ideation: The Effect of Brain-Derived Neurotrophic Factor Polymorphism and Social Support

“…44 For example, the Met allele frequency of the Korean participants was relatively higher than other races. 55 The allele frequency in our study (PTSD, 67.5%; HCs, 69.1%) was like previous studies conducted on Korean participants (63.64%-71.64%). 56 Second, the moderation effect of social support was significant in the relationship between childhood physical abuse and suicidal ideation in the HCs.…”

BDNF Genetic Variant and Its Genotypic Fluctuation in Major Depressive Disorder

“…In Brazil, Schenkel et al [53] related "suicide attempts" to the A (Met) allele rather than the G (Val) allele. Interestingly, Korean participants presented mixed results [54][55][56][57], demonstrating a lack of consensus on this association. Although no significant association between the BDNF genetic variant and the "attempted suicide" variable in a Chinese study (p = 0:807), Brunoni et al [19] found low BDNF protein serum levels might be related to attempted suicide [22].…”

“…The BDNF gene and its protein levels may be affected by life's adversities and suicide attempts [16,53,57], proving that environmental and genetic factors go together for MDD development. Regardless, additional studies in different populations are necessary to reduce the controversies regarding these variables' association [54,56,57,62].…”

Investigation of polymorphic variants of SLC6A4, TPH-1, and TPH-2 genes in cases of completed suicide

“…These studies have typically investigated the psychiatric, sociological, economic, and biological components of suicidal behavior. There are also studies on the genetic component of suicidal behavior [12][13][14][15][16][17]. Monozygotic and dizygotic twins were investigated in the initial studies on the genetic component of this behavior [18].…”

“…It has been shown that monozygotic twins are more likely to exhibit suicidal behavior than dizygotic twins [18][19][20]. Additionally, family studies and studies performed on adopted individuals [21][22][23][24][25], have shed light on molecular etiologies for suicide behavior [12][13][14][15][16][17].…”