Association Between Sirtuin 1 (SIRT1) Gene Polymorphisms and Suicide Attempts in Schizophrenia: An Exploratory Study

Abstract

Objective: Schizophrenia is a neuropsychiatric disorder with a high risk of suicide, arising from the interplay between genetic predisposition and environmental factors. The Sirtuin 1 (SIRT1) gene, an NAD+- dependent deacetylase, is involved in cellular stress response, apoptosis, and mitochondrial functions, as well as neuroprotection and circadian rhythm regulation. SIRT1 is thought to influence neurobiological mechanisms related to cognitive and affective regulation. This study aimed to investigate the association between specific SIRT1 gene polymorphisms and suicide attempts in patients with schizophrenia. Methods: This cross-sectional, observational genetic association study included only a case group comprising 100 patients diagnosed with schizophrenia. Targeted sequencing of the SIRT1 gene, encompassing all coding exons and their exon-intron junctions, was performed. Based on minor allele frequency and technical quality criteria, 10 single nucleotide polymorphisms (SNPs) were selected for further analysis. Linkage disequilibrium (LD) assessment, haplotype structure, and genetic modeling were conducted using the SHEsis software platform. Results: The rs10997870 GG genotype (p=0.017) and the rs7896005 AA genotype (p=0.033) were associated with suicide attempts, whereas the rs2236318 A allele (p=0.015) and the rs41299232 GG genotype (p=0.027) were found to be protective. The C-T-A-G haplotype (p=0.005) was associated with an increased risk, while the G-A-G-T haplotype (p=0.032) showed a protective effect. Conclusion: Certain polymorphisms and haplotypes within the SIRT1 gene may be associated with suicide risk among patients with schizophrenia. These findings point to the potential role of genetic profiling in identifying high-risk individuals. Further large-scale studies are warranted to increase the generalizability of the findings and to elucidate the underlying mechanisms in greater detail.