Sequence analysis of five exons of SLC6A4 gene in Mexican patients with anorexia nervosa and bulimia nervosa

• Published in: Gene Vol. 748; p. 144675
• Main Authors: Hernández-Muñoz, S., Camarena-Medellin, B., González-Macías, L., Aguilar-García, A., Flores-Flores, G., Luna Dominguez, D., Azaola-Espinosa, A., Flores-Ramos, M., Caballero-Romo, A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.07.2020
• Subjects: anorexia; Anorexia Nervosa; Bulimia Nervosa; DNA; Exons; gain-of-function mutation; Genetic variants; sequence analysis; Sequencing; serotonin; Serotonin transporter; SLC6A4; Anorexia Nervosa; Serotonin transporter; Bulimia Nervosa; Exons; Genetic variants; Sequencing; SLC6A4
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2020.144675

•Gene variants of SLC6A4 are associated with eating disorders.•SLC6A4 gene variants are related with a possible damaging or gain-of-function.•SLC6A4 gene are related with the susceptibility to develop restrictive-eating and BN-binge-eating behaviors. Accumulating evidence indicates that alterations in the serotonin system are related to changes in eating behavior. The serotonin transporter is encoded by the SLC6A4 gene and has been an interesting candidate for anorexia nervosa- restrictive type (AN-R) and bulimia nervosa (BN). Interestingly, functional variants have been identified in the coding region that could contribute to understand the role of this gene in eating disorders. The aim was to identify genetic variants in five exons of SLC6A4 gene using Sanger-sequencing in anorexia nervosa-restrictive and bulimia nervosa patients, and a control group. The sample consisted of 86 patients and 50 control subjects. We obtained DNA samples from all subjects and performed Sanger-sequence analysis of the 1, 2, 3, 8 and 9 exons. The sequences were compared with the reference sequence of the SLC6A4 gene. The sequence analysis of the five exons of the gene identified several variants. In the AN-R, we observed two novel variants (g.130delA and c.1740G > A), three synonymous variants (rs57172732, rs55908624, rs74478645) and a missense variant (L90F) reporting a probably deleterious and damaging variant. In BN, we identified two novel variants (g.295C > G and c.1725G > A), and the non-synonymous (rs28914832/I425V), reported as benign. Interestingly, we observed the 425V variant in three patients in the BN, variant that previously was reported in patients with a spectrum obsessive–compulsive disorder. The results of our study suggest that variants of the SLC6A4 gene are related with a possible damaging or gain-of-function and may be involved in the susceptibility to AN-R and BN patients. However, the present findings should be considered as preliminary until replicated in large samples.