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.
Keywords: Haplotypes, schizophrenia, single nucleotide polymorphism,
sirtuins, suicide attempt