SLC6A3 (DAT1) as a Novel Candidate Biomarker Gene for Suicidal Behavior.

It has been previously shown that the serotonin and dopamine neurotransmitter systems might influence the predisposition to suicidal behavior. This study aims to estimate the contribution of 11 polymorphisms in the genes SLC6A4 (5HTT), HTR1A, HTR2A, HTR1B, SLC6A3 (DAT1), DRD4, DRD2, COMT, and BDNF to suicidal behavior and severity of symptoms of depression and anxiety in the Russian population. The study was performed on 100 patients with repeated suicide attempts and 154 controls. We first found an association between SLC6A3 (DAT1) 40 bp VNTR locus and suicidal behavior. This association was significant; when using the codominant (p = 0.006), dominant (p = 0.001), overdominant (p = 0.004), and log-additive (p = 0.004) models, LL genotype played a protective role (OR = 0.48, 0.29-0.82, p = 0.005). Difference in the distribution of COMT rs4680 genotypes was significant in the codominant (p = 0.04), dominant (p = 0.013), and log-additive (p = 0.02) models, and AA genotype might protect against suicide (OR = 0.49, 0.26-0.91, p = 0.025). SLC6A4 5-HTTLPR + rs25531 locus was significant in the recessive model (p = 0.024), and also affected the severity of symptoms of depression (p = 0.044) and personal anxiety (p = 0.029). Our results suggest that allelic variants of SLC6A3, COMT, and SLC6A4 genes might be considered as risk factors for suicidal attempts.

Polymorphisms of dopamine receptor genes DRD2 and DRD4 in African populations of Hadza and Datoga differing in the level of culturally permitted aggression.

The key regulator in the control of aggressive behavior is dopamine receptors. Association of variants in these genes with aggression has been shown in modern populations. However, these studies have not been conducted in traditional cultures. The aim of our study was to investigate population features in distributions of allele and genotype frequencies of DRD2 rs1800497, DRD4 120 bp Ins, and DRD4 exon III polymorphisms and their associations with aggressive behavior in the traditional African populations of Hadza and Datoga, which display a contrast in their culturally permitted aggression. Overall, 820 healthy unrelated Hadza and Datoga individuals were studied. Self-rated scores of aggression were collected using Buss and Perry's Aggression Questionnaire. Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype of each individual. We show that the Hadza and the Datoga differed significantly in allele and genotype frequencies of all studied loci. Our association analysis detected that only ethnicity and sex of individuals significantly influenced their aggression rank, but we failed to identify any associations of DRD2 rs1800497, DRD4 120 bp Ins, or DRD4 exon III polymorphisms with aggression. Thus, our data have no strong evidence to support the involvement of polymorphisms of DRD2 and DRD4 in controlling aggressive behavior.