Key result
The APOE rs405509 variant demonstrated a significantly higher homozygous minor allele frequency in Bangladeshi males compared to females (17.5% vs 5.5%, P=0.05), indicating gender-specific dementia risk.
Why the study?
Alzheimer disease and related dementias exhibit significant gender disparities in prevalence and progression, but the genetic underpinnings of these differences remain incompletely understood in the Bangladeshi population.
Do gender-specific allelic variation patterns affect dementia susceptibility in the Bangladeshi population?
Case-Control (n=112)
No
Do gender-specific allelic variation patterns affect dementia susceptibility in the Bangladeshi population?
Absolute Event Rate: 17.5% vs 5.5%
p-value: p=0.05
The study identifies potential gender-specific genetic variants (APOE rs405509 and BDNF rs6265) associated with dementia susceptibility in the Bangladeshi population, highlighting the need for sex-stratified risk assessment.
Suggests gender-specific AD genetic patterns in Bangladeshi patients; hypothesis-generating and requires replication before clinical use.
Background: Alzheimer’s disease (AD) and related dementias exhibit significant gender disparities in prevalence and progression, yet the genetic underpinnings of these differences remain incompletely understood. We aimed to observe gender-specific allelic variation patterns in key dementia susceptibility genes among the Bangladeshi population. Methods: The Community Awareness and Research on Early Dementia (CARED) study is a case-control study that recruited age- and gender-adjusted AD patients and healthy controls aged ≥ 18 years between 2022 and 2024. We conducted a next-generation sequencing (NGS) analysis of 112 individuals (57 males and 55 females), focusing on key genes associated with dementia susceptibility. Chi-square tests were used to assess gender-specific allele frequency differences for each variant. While Bonferroni-corrected thresholds are noted for reference, nominal P-values are reported due to the study’s exploratory design and limited sample size. Results: The NGS analysis of dementia-associated variants found distinct genotype distribution patterns for Apolipoprotein E (APOE) (rs429358, rs7412, and rs405509), Brain-Derived Neurotrophic Factor (BDNF) (rs6265), and Catechol-O-methyltransferase (COMT) (rs4680) in males and females. We observed a higher minor allele frequency (MAF) of APOE rs429358 in females than males (23.7% vs 15.8%), while APOE rs405509 showed a stronger effect in males, with a significantly higher homozygous MAF (17.5% vs 5.5%, P = 0.05). The BDNF variant rs6265 also showed a greater prevalence in males, with a higher proportion of homozygous carriers (10.7% vs 3.8%) than in females. Linkage disequilibrium (LD) analysis revealed a strong association between APOE rs429358 and rs7412 (r² =0.85), with a rapid decay in LD beyond 10 kb (mean r² =0.15) in the APOE region. Conclusion: We identified APOE rs405509 and BDNF rs6265 as potential genetic variants associated with gender-specific susceptibility to dementia among Bangladeshis. Additionally, APOE variants rs429358 and rs7412 exhibited strong linkage disequilibrium, with rapid decay from the APOE locus, indicating a higher rate of genetic mixing in this population. Given the exploratory nature of this study, large-scale validation is warranted to confirm these findings.
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Ranjan et al. (2025) conducted a case-control in Dementia and Alzheimer's disease (n=112). Male gender vs. Female gender was evaluated on Homozygous minor allele frequency of APOE rs405509 (p=0.05). The APOE rs405509 variant demonstrated a significantly higher homozygous minor allele frequency in Bangladeshi males compared to females (17.5% vs 5.5%, P=0.05), indicating gender-specific dementia risk.
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