Association between the SLC6A4 gene and schizophrenia: an updated meta-analysis

BACKGROUND: In order to explore the association between the SLC6A4 gene and the risk of schizophrenia, an updated meta-analysis was conducted using a total of 46 scientific articles. METHODS: Through a literature search, papers studied included 35 articles on serotonin-transporter-linked polymorphic region (5-HTTLPR) with 8,752 cases and 10,610 controls, 17 articles on second intron variable number of tandem repeats with 7,284 cases and 8,544 controls, four studies on rs1042173 with 1,351 cases and 2,101 controls, and four studies on rs140700 with 1,770 cases and 2,386 controls. Pooled, subgroup, and sensitivity analyses were performed, and the results were visualized by forest and funnel plots. RESULTS: An association between 5-HTTLPR and the risk of schizophrenia was not found, except for an Indian subgroup analysis (P(z)=0.014, OR =1.749, 95% CI =1.120–2.731). A 10 repeats/12 repeats (10R/12R) genotype was a protective factor against schizophrenia (P(z)=0.020, OR =0.789, 95% CI =0.646–0.963), but a 12R/12R genotype was a risk factor for schizophrenia (P(z)=0.004, OR =1.936, 95% CI =1.238–3.029) in the pooled analyses. In Caucasians, a GG genotype of rs1042173 may be a risk factor for schizophrenia (P(z)=0.006, OR =1.299, 95% CI =1.079–1.565). No association was found between rs140700 and the risk for schizophrenia. CONCLUSION: Through meta-analysis, we were able to gain insight into previously reported associations between SLC6A4 polymorphism and schizophrenia.