Association of HTTLPR, BDNF, and FTO Genetic Variants with Completed Suicide in Slovakia

Overview

Journal J Pers Med

Date 2023 Mar 29

PMID 36983683

Authors

Aneta Bednarova

Viera Habalova

Silvia Farkasova Iannaccone

Ivan Tkac

Dominika Jarcuskova

Michaela Krivosova

Matteo Marcatili

Natasa Hlavacova

Affiliations

Soon will be listed here.

Abstract

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes (rs6265, rs962369), (), and (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide.

Citing Articles

rs962369 Is Associated with Major Depressive Disorder.

Bednarova A, Habalova V, Tkac I Biomedicines. 2023; 11(8).

PMID: 37626739 PMC: 10452342. DOI: 10.3390/biomedicines11082243.

Association Study of , , and Genetic Variants with Schizophrenia Spectrum Disorders.

Bednarova A, Habalova V, Krivosova M, Marcatili M, Tkac I J Pers Med. 2023; 13(4).

PMID: 37109044 PMC: 10141144. DOI: 10.3390/jpm13040658.

References

Scuteri A, Sanna S, Chen W, Uda M, Albai G, Strait J . Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007; 3(7):e115. PMC: 1934391. DOI: 10.1371/journal.pgen.0030115. View

Perroud N, Aitchison K, Uher R, Smith R, Huezo-Diaz P, Marusic A . Genetic predictors of increase in suicidal ideation during antidepressant treatment in the GENDEP project. Neuropsychopharmacology. 2009; 34(12):2517-28. DOI: 10.1038/npp.2009.81. View

Schosser A, Carlberg L, Calati R, Serretti A, Massat I, Spindelegger C . The Impact of BDNF Polymorphisms on Suicidality in Treatment-Resistant Major Depressive Disorder: A European Multicenter Study. Int J Neuropsychopharmacol. 2017; 20(10):782-787. PMC: 5632306. DOI: 10.1093/ijnp/pyx028. View

Yao Y, Wen Y, Du T, Sun N, Deng H, Ryan J . Meta-analysis indicates that SNP rs9939609 within FTO is not associated with major depressive disorder (MDD) in Asian population. J Affect Disord. 2016; 193:27-30. DOI: 10.1016/j.jad.2015.12.048. View

Fanaei H, Karimian S, Sadeghipour H, Hassanzade G, Kasaeian A, Attari F . Testosterone enhances functional recovery after stroke through promotion of antioxidant defenses, BDNF levels and neurogenesis in male rats. Brain Res. 2014; 1558:74-83. DOI: 10.1016/j.brainres.2014.02.028. View

Widagdo J, Zhao Q, Kempen M, Tan M, Ratnu V, Wei W . Experience-Dependent Accumulation of N6-Methyladenosine in the Prefrontal Cortex Is Associated with Memory Processes in Mice. J Neurosci. 2016; 36(25):6771-7. PMC: 4916251. DOI: 10.1523/JNEUROSCI.4053-15.2016. View

Pungercic G, Videtic A, Pestotnik A, Zupanic Pajnic I, Zupanc T, Balazic J . Serotonin transporter gene promoter (5-HTTLPR) and intron 2 (VNTR) polymorphisms: a study on Slovenian population of suicide victims. Psychiatr Genet. 2006; 16(5):187-91. DOI: 10.1097/01.ypg.0000218617.65633.9e. View

Monteggia L, Luikart B, Barrot M, Theobold D, Malkovska I, Nef S . Brain-derived neurotrophic factor conditional knockouts show gender differences in depression-related behaviors. Biol Psychiatry. 2006; 61(2):187-97. DOI: 10.1016/j.biopsych.2006.03.021. View

Luppino F, de Wit L, Bouvy P, Stijnen T, Cuijpers P, Penninx B . Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. 2010; 67(3):220-9. DOI: 10.1001/archgenpsychiatry.2010.2. View

10.

Chojnicka I, Fudalej S, Walczak A, Wasilewska K, Fudalej M, Stawinski P . Inverse association between obesity predisposing FTO genotype and completed suicide. PLoS One. 2014; 9(9):e108900. PMC: 4181953. DOI: 10.1371/journal.pone.0108900. View

11.

Frayling T, Timpson N, Weedon M, Zeggini E, Freathy R, Lindgren C . A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007; 316(5826):889-94. PMC: 2646098. DOI: 10.1126/science.1141634. View

12.

Zarza-Rebollo J, Molina E, Rivera M . The role of the FTO gene in the relationship between depression and obesity. A systematic review. Neurosci Biobehav Rev. 2021; 127:630-637. DOI: 10.1016/j.neubiorev.2021.05.013. View

13.

Hess M, Hess S, Meyer K, Verhagen L, Koch L, Bronneke H . The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat Neurosci. 2013; 16(8):1042-8. DOI: 10.1038/nn.3449. View

14.

Schild A, Pietschnig J, Tran U, Voracek M . Genetic association studies between SNPs and suicidal behavior: a meta-analytical field synopsis. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 46:36-42. DOI: 10.1016/j.pnpbp.2013.06.014. View

15.

Hawton K, van Heeringen K . Suicide. Lancet. 2009; 373(9672):1372-81. DOI: 10.1016/S0140-6736(09)60372-X. View

16.

Du T, Rao S, Wu L, Ye N, Liu Z, Hu H . An association study of the m6A genes with major depressive disorder in Chinese Han population. J Affect Disord. 2015; 183:279-86. DOI: 10.1016/j.jad.2015.05.025. View

17.

Murakami F, Shimomura T, Kotani K, Ikawa S, Nanba E, Adachi K . Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese. J Hum Genet. 1999; 44(1):15-7. DOI: 10.1007/s100380050098. View

18.

Wray N, Ripke S, Mattheisen M, Trzaskowski M, Byrne E, Abdellaoui A . Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018; 50(5):668-681. PMC: 5934326. DOI: 10.1038/s41588-018-0090-3. View

19.

Zarrilli F, Angiolillo A, Castaldo G, Chiariotti L, Keller S, Sacchetti S . Brain derived neurotrophic factor (BDNF) genetic polymorphism (Val66Met) in suicide: a study of 512 cases. Am J Med Genet B Neuropsychiatr Genet. 2008; 150B(4):599-600. DOI: 10.1002/ajmg.b.30849. View

20.

Gaysina D, Zainullina A, Gabdulhakov R, Khusnutdinova E . The serotonin transporter gene: polymorphism and haplotype analysis in Russian suicide attempters. Neuropsychobiology. 2006; 54(1):70-4. DOI: 10.1159/000096041. View