Date of Award

12-20-2024

Degree Type

Thesis

Degree Name

MPhil in Biological and Biomedical Sciences

First Advisor

Dr. Syeda Sadia Fatima

Second Advisor

Dr Irfan Hussain

Third Advisor

Ms. Sabah Farhat

Department

Biological and Biomedical Sciences

Abstract

Introduction: Metabolic syndrome, marked by conditions such as hypertension, insulin resistance, and dyslipidemia, is not only prevalent worldwide but also shows a significant association with depression. Depression, a pervasive global health concern affecting over 280 million people, exhibits a positive relationship with metabolic syndrome. Shared genetic factors are hypothesized to underlie this connection. This proof-of-concept pilot study aims to investigate the frequency of depression by different screening tools and identify possible connections between depression and metabolic syndrome, focusing on the satiety-regulating genes Prolactin, Oxytocin, and Neuropeptide Y.
Methods: A cross-sectional proof of concept study was conducted for the duration of 6 months at the Aga Khan University. Data collection included demographic assessments, depression screening using Beck's Depression Inventory (BDI), DSM V and PHQ9. Subsequently genetic analysis was done through DNA extraction, conventional PCR, and sanger sequencing. Mutation analysis was conducted using NCBI data base. The Oxytocin structure was predicted through online alphafold version 2 server. Statistical analyses were applied using SPSS version 20. Data was presented as Mean±SEM and student t test was applied to assess differences in mean. Chi square statistics were used for gene frequency. In all instances a p value of < 0.05 was considered significant.
Results: The study revealed that the average age of participants was 30.31 years, with 52% being male . Among the participants, 64% were healthy controls, While 35% had metabolic syndrome (MetS).Subject with Mets and a Beck Depression Inventory(BDI) score>20 exhibited higher body fat percentages(39.22%) and elevated blood glucose levels, along with lower HDL cholesterol levels. Depression was more prevalent in participant aged 30 years or older, particularly in males with MetS. Correlation analysis showed significant positive associations between depression and body fat percentage, random blood glucose, HDL cholesterol and blood pressure, while strong negative correlation was observed with triglycerides. Genotype analysis indicated a higher frequency of the C allele of the NPY SNP in MetS subjects and those with depression, suggesting a link with more severe forms of depression and schizophrenia. The PRL SNP showed similar allele frequencies across all groups, regardless of MetS or depression status. These finding underscores the complex interplay between metabolic health, genetic factors, and mental health, highlighting the need for integrated approaches in managing these conditions. Comprehensive bioinformatics analysis of the OXT gene across four population (CEU, CHB, YRI and LWK) revealed genetic variation consistent with neutral evolution, as indicated by statistics such as Tajima’s D, Fu and Li’s D and Fay and Wu’s H along with low F_ST values. This suggests that neither positive nor balancing selection has significantly influenced the OXT gene or its surrounding region. Hence, there exist neutral evolution in the oxytocin/neurophysin I gene across human populations. Additionally, we analyzed ten OXT gene variants with CADD scores over 20.0, including seven highly deleterious variants (CADD >30) with mutations such as stop-gained and frameshift. This suggest significant functional impact on oxytocin production or function.
Conclusion: The findings underscore the complex interplay between metabolic health, genetic factors and mental health, emphasizing the need for integrated approaches in managing these conditions. The study also suggests that the OXT gene has evolved neutrally across human population, with certain variants potentially impacting oxytocin function significantly.

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1

Last Page

72

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