Preliminary Research Report on the Relationship between CYP46A1 Polymorphism and Suicide Risk

Research Background

Suicide, defined as the intentional act of ending one’s own life, is a major global public health issue. The incidence of suicide is higher among individuals with Major Depressive Disorder (MDD). However, the role of cholesterol in suicide risk remains controversial, prompting researchers to explore potential genetic markers. This study focuses on the relationship between CYP46A1 gene polymorphisms, particularly SNPs (Single Nucleotide Polymorphisms) rs754203 and rs4900442, and suicide risk. Previous studies have suggested that these SNPs may be relevant in type 2 diabetes and neurodegenerative diseases such as Alzheimer’s, but their role in suicide has not been clearly established.

Research Source

This study was jointly conducted by María Fernanda Serna-Rodríguez, Oscar Cienfuegos-Jiménez, Ricardo Martín Cerda-Flores, and other authors, primarily from various departments at the Autonomous University of Nuevo Leon, Mexico. The research was published in the journal “Neuromolecular Medicine” Volume 26, Issue 11, 2024. The study was received on January 11, 2024, and accepted for publication on March 1, 2024.

Research Process

Study Subjects and Sample Collection

This study was conducted from August 2017 to August 2022 at the “Jose Eleuterio Gonzalez” University Hospital in Mexico, divided into three groups: suicide death victims (188), patients with MDD only (126), and a control group without suicidal behavior (144). Samples from suicide victims were collected postmortem at the hospital’s forensic department, while other participants were recruited from the psychiatric department.

Sample size calculation was performed using EpiTools, based on the Minor Allele Frequency (MAF) of CYP46A1 polymorphisms, with an expected sample size of about 160 people per SNP. However, due to the COVID-19 pandemic, sample recruitment was affected, resulting in a final total analysis of 458 individuals.

DNA Extraction and Genotyping

DNA was extracted from each sample according to the manufacturer’s instructions, and genotyping of CYP46A1 rs754203 and rs4900442 was performed using TaqMan SNP genotyping assays on the StepOnePlus™ Real-Time PCR System. DNA quality and concentration were initially evaluated using a nanodrop spectrophotometer.

Data Analysis

Descriptive statistics were used to characterize the samples, with t-tests or ANOVA used to test differences between the three groups. A retrospective power analysis assuming a medium effect size and an α level of 0.05 showed a detection rate of approximately 99.9% for this study. Genotype distributions were tested for Hardy-Weinberg equilibrium, and allele frequencies and genotype odds ratios (OR) with 95% confidence intervals (CI) were calculated. Statistical analysis was performed using SPSS 27.0.

Research Results

Clinical and Demographic Characteristics

The mean ages for the three groups were: 36.42 ± 16.93 years for the suicide death group, 33.10 ± 14.55 years for the MDD patient group, and 30.41 ± 12.40 years for the control group. The control group had significantly more years of education than the patient groups. Religious beliefs showed no significant impact. BDI (Beck Depression Inventory) scores were significantly higher in the patient group (16.09 ± 12.15) compared to the control group (4.74 ± 4.14).

Genotype and Allele Distribution

The study found that the g/g genotype of CYP46A1 rs754203 SNP was significantly associated with suicide, with the g allele increasing suicide risk by 37% (OR = 1.370, 95% CI = 1.002–1.873). However, no significant differences were observed for the rs4900442 SNP.

Gender Difference Analysis

In males, the a/g heterozygous genotype of rs754203 SNP was significantly associated with suicide, suggesting that gender may play an important role in genetic susceptibility. No significant differences were found in females.

Distribution in MDD Patients and Control Group

No significant associations were found between the two polymorphisms in MDD patients compared to the control group, indicating a more complex relationship between these genetic markers and depression-related suicide risk.

Research Conclusions

This study is the first to explore the relationship between CYP46A1 rs754203 and rs4900442 polymorphisms with suicide and major depressive disorder. The results suggest that carriers of the g allele of rs754203, especially in males, have an increased risk of suicide, highlighting the importance of gender-specific genetic risk factors in psychiatric disorder research. However, rs4900442 showed no significant association with suicide or MDD, adding to our understanding of the complex genetic architecture of suicide.

Significance of the Research

The importance of this study lies in the discovery of associations between certain variations in the CYP46A1 gene and suicide risk. These results not only provide new clues for genetic research in mental disorders but also emphasize the need for more individualized and gender-differentiated research approaches. Future studies can further validate these findings through more diverse samples and cross-ethnic research, exploring the interactions between genetic markers and environmental factors to better understand the genetic basis of suicidal behavior.

Research Highlights

• Discovered a significant association between CYP46A1 rs754203 polymorphism and suicide risk, particularly in males.
• Emphasized the importance of gender differences in genetic research of mental disorders.
• Provided potential value for genetic screening in predicting and preventing suicide.

This study offers a new perspective for understanding the complex genetic basis of suicide, contributing to the development of more effective risk assessment and intervention strategies.