Association of DRD2, 5-HTTLPR, and 5-HTTVNTR Gene Polymorphisms With Posttraumatic Stress Disorder in Tibetan Adolescents: A Case–Control Study

Abstract

Background: Earthquake exposure is a source of stress, yet only a minority of survivors experience clinically meaningful disturbance in psychological function. Genetic epidemiological research has found that posttraumatic stress disorder (PTSD) symptoms are associated with genetic factors. Further research to reveal which genetic loci relate to the development of PTSD is warranted. Method: We investigated the relationships between PTSD and the dopamine D2 receptor ( DRD2) gene Taq I polymorphism and the serotonin transporter gene ( SCL6A4) polymorphisms 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) and 5-HTTVNTR in 565 adolescent earthquake survivors. PTSD-positive adolescents were identified using the PTSD Checklist–Civilian Version and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders 4. Genotypes were analyzed using the polymerase chain reaction—restriction fragment length polymorphism analysis. The Pearson χ2 test was used to investigate the differences in genotype and allele frequencies between case and control groups. Binary logistic regression analysis was performed to identify possible influencing factors for PTSD. Results: The DRD2 Taq I and 5-HTTVNTR polymorphisms had statistically significant effects on PTSD, while 5-HTTLPR did not. Specifically, the DRD2 Taq I A1 allele was highly positively correlated with PTSD, whereas the 10 allele of 5-HTTVNTR was negatively correlated. Conclusions: These data suggest that the DRD2 Taq I and 5-HTTVNTR genotypes moderate sensitivity to stress and the expression of emotional disturbance involving PTSD symptoms. These findings have important implications for PTSD etiology as well as for both primary prevention and treatment strategies.

The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda

“…In contrast to previous findings of associations between 5-HTTLPR and STin2 VNTR and IMDs (Battersby et al, 1996;Evans et al, 2013;Gressier et al, 2013;Zhao et al, 2013;Smoller, 2016;Wang et al, 2016;Xiao et al, 2019), we found no direct association between any of the investigated SLC6A4 polymorphisms and IMDs. This may be due to the complex nature of IMDs, where many genetic variants contribute to disease risk, each contributing a small effect (Plomin and Davis, 2009) and thus the effect of a few variants may not be powerful enough to show significant association.…”

“…This may be due to the complex nature of IMDs, where many genetic variants contribute to disease risk, each contributing a small effect (Plomin and Davis, 2009) and thus the effect of a few variants may not be powerful enough to show significant association. Indeed, studies examining the contributions of 5-HTTLPR and STin2 variants have yielded inconsistent results, with other published work similarly failing to find a significant association (Munafò et al, 2009a,b;Culverhouse et al, 2018;Xiao et al, 2019). In order to resolve these contradictory results, studies looking at epistatic interactions are required.…”

“…The STin2 VNTR polymorphism has also been found to interact with 5-HTTLPR to regulate expression of SLC6A4, with the combination of the 5-HTTLPR S-allele and either STin2.10 or STin2.12 associated with increased expression, as compared to STin2.9 whose combination with 5-HTTLPR S-allele directed expression levels comparable to the 5-HTTLPR S-allele alone (Ali et al, 2010;Haddley et al, 2012). The STin2.9 allele has been associated with anxiety in patients with selfharming behaviors (Evans et al, 2013), STin2.10 has been associated with both anxiety and PTSD (Evans, Li and Whipple, 2013;Xiao et al, 2019) and the STin2.12 allele has been associated with depression, neuroticism, and suicide (Lopez de Lara et al, 2007;O'Gara et al, 2008;Kalungi et al, 2017).…”

DRD2 TaqI A polymorphism in Eastern Uttar Pradesh population

“…Taq1A polymorphism was very well studied in world's different populations [3,5,9,15,16] as well as in different Indian regions [17][18][19][20][21][22][23][24][25][26][27]. Various studies reported presence of A1 allele is significantly higher in certain drug of abuse such as alcoholism and other behavioural characteristics as well [28].…”

“…Several polymorphisms are reported in DRD2 gene (Taq1 B, Taq1D, -141 Ins/Del, Ser-Cys(S311C) but Taq1 A polymorphism is well studied in different psychiatric disorders including schizophrenia [5], depression [6], bipolar disorder [7], ADHD [8], and PTSD [9] and drug abuse [3] . TaqI A is SNP (rs1800497) located 9.8 kb downstream of DRD2 gene within exon 8 of functionally unrelated neighbouring gene, Ankyrin repeat and kinase domain containing-1(ANNK1).…”