Influence of 5-HTTLPR and 5-HTTVNTR polymorphisms of the serotonin transporter gene (SLC6A4) on major depressive disorder in a sample of Argentinean population

Abstract

Variations in the serotonin transporter gene (SLC6A4) have been implicated in a wide range of neuropsychiatric disorders such as major depression. However, the results are still controversial. A polymorphism in SLC6A4 gene characterized by an insertion/deletion of 44 bp (5-HTTLPR) in the promoter region (alleles L and S) and a variable number of tandem repeats polymorphism (5-HTTVNTR) in intron 2 (common alleles: 10 and 12) (Lesch et al., 1994) would present a differential regulatory effect on gene transcription.The association between these polymorphisms and major depression was analysed in 95 patients and 107 healthy controls in a sample of Argentinean population. This protocol has been approved by an independent Bioethic board. All the genotypes were obtained by standard procedures (Assal et al., 2004).Patients and controls were interviewed based on diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Hamilton depression scale, self-administered Beck scale and MINI structured diagnostic interview. Only patients with Hamilton depression scale greater than 18 points were included.The comparison of frequencies was carried out through logistic regression. A multiple testing correction was applied.The frequencies in patients and controls for both markers were in Hardy-Weingberg equilibrium (cases: L/L = 22%; L/S = 54%; S/S = 24%; controls: L/L = 27.1%; L/S = 52.3%; S/S = 20.6% and cases: 12/12 = 39%; 12/10 = 54%; 10/10 = 7%; controls: 12/12 = 46%; 12/10 = 42%; 10/10 = 12%).The linkage disequilibrium between polymorphisms was evaluated (D 0 = 0.29; r 2 = 0.04). The results indicate an independent distribution of the polymorphic loci; others authors observed the low rate of linkage between the 5-HTTLPR polymorphism and other polymorphisms could be due to recombination events in hot-spots located in the first intron. When a single marker association was evaluated between patients and controls, no significant differences were found. However, considering the findings of Hranilovic et al. 2004, a combinatorial effect of both polymorphisms is considered to be possible. The genotypes were grouped and compared according to their expression levels (no low expression at both loci, 11% vs. 6%; low expression at one locus: 40% vs. 60%; low expression at both loci: 49% vs. 34%, patients vs. controls, respectively). Although genotypes of the low expression group at one locus would confer protection with P = 0.005 [corrected P < 0.03; odds ratio (OR) = 0.45, 95% confidence interval (CI) = (0.25-0.78)], genotypes of the low expression group in both loci would confer risk with a P = 0.02 [corrected P < 0.03; OR = 1.93, 95% CI = (1.1-3.4)]. There are differences between the groups regarding their carrier status (being or not carriers of risk alleles S and 10). Those individuals carrying S and 10 alleles have an increased risk of having the depressive phenotype.We think it is necessary to increase not only the number of local individuals but also the number of markers under analysis. It shou...

The role of 5-HTTLPR in autism spectrum disorder: New evidence and a meta-analysis of this polymorphism in Latin American population with psychiatric disorders

“…Recognizing the under-representation of Latin American population in studies aimed to understand the role of 5-HTTLPR on worldwide [26,27,29], here we present a meta-analysis including articles which evaluate this polymorphism in Latin American individuals with psychiatric disorders as ASD, bipolar disorder, major depressive disorder, obsessive compulsive disorder, attention deficit hyperactive disorder, schizophrenia, dysthymia, anxiety disorder and suicide [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. Although the S allele has been associated with increased risk for psychiatric disorders [16][17][18][19][20][21]55], our meta-analysis revealed no significant heterogeneity among studies, no publication bias and failed to find an association between 5-HTTLPR and a risk for psychiatric disorders.…”