Association between serotonin transporter gene polymorphisms and increased suicidal risk among HIV positive patients in Uganda

Abstract

BackgroundPersons living with HIV/AIDS (PLWHA) are at an increased risk of suicide. Increased suicidal risk is a predictor of future attempted and completed suicides and has been associated with poor quality of life and poor adherence with antiretroviral therapy. Clinical risk factors have low predictive value for suicide, hence the interest in potential neurobiological correlates and specific heritable markers of suicide vulnerability. The serotonin transporter gene has previously been implicated in the aetiology of increased suicidal risk in non-HIV infected study populations and its variations may provide a platform for identifying genetic risk for suicidality among PLWHA. The present cross-sectional study aimed at identifying two common genetic variants of the serotonin transporter gene and their association with increased suicidal risk among human immunodeficiency virus (HIV)-positive adults in Uganda.ResultsThe prevalence of increased suicidal risk (defined as moderate to high risk suicidality on the suicidality module of the Mini Neuropsychiatric Interview (M.I.N.I) was 3.3% (95% CI, 2.0–5.3). The 5-HTTLPR was found to be associated with increased suicidal risk before Bonferroni correction (p-value = 0.0174). A protective effect on increased suicidal risk was found for the 5-HTTLPR/rs25531 S A allele (p-value = 0.0046)- which directs reduced expression of the serotonin transporter gene (5-HTT).ConclusionThe S A allele at the 5-HTTLPR/rs25531 locus is associated with increased suicidal risk among Ugandan PLWHA. Further studies are needed to validate this finding in Ugandan and other sub-Saharan samples.

Suicide in a rural area of coastal Kenya

“…In the US, suicide rates are a function of sex, age and race where the risk for white men increases continuously with age while that of their black counterparts shows a pattern similar to that of the KHDSS [ 24 ]. The similarity in patterns between the black population in the US and the KHDSS population might suggest a genetic link to suicidal tendencies, backing growing evidence on genetic links of suicidal behaviour [ 25 ].…”

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

“…The 5-HTTLPR, 5-HTTLPR-rs25531, and STin2 VNTR polymorphisms were genotyped following a procedure described by Kalungi et al (2017). Fragment sizes revealed by PCR were confirmed by restriction fragment length analysis on the ABI prism.…”

“…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).…”

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

“…SLC6A4 is located on chromosome 17, 17q11.1-q12 [37]. Polymorphisms in SLC6A4 that have been considered as a risk factor for suicidal behavior are 5HTTLPR, S-Tin2, rs25531, and rs6355 [38][39][40][41]. In rhesus macaques, the short allele ("s") of 5HTTLPR is associated with decreased serotonergic function among monkeys reared in stressful conditions [42,43].…”