Date of Award

11-2025

Degree Type

Thesis

Degree Name

MPhil in Biological and Biomedical Sciences

First Advisor

Dr. Syeda Sadia Fatima

Second Advisor

Dr. Paras Jawaid

Third Advisor

Dr. Bushra Bilal

Department

Biological and Biomedical Sciences

Abstract

Introduction: Metabolic syndrome (Mets) is a group of conditions, such as hypertension, dyslipidemia, insulin resistance, and obesity that increase the risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). As per the International Diabetes Federation (IDF), approximately one-third of the global population is affected by Mets. Moreover, 2024 IDF statistics demonstrate the significant public health crisis with growing prevalence of diabetes to an estimated 34.5 million individuals in the Middle East and North Africa (MENA) region; notably, Pakistan holds the fourth rank across the globe.
Objectives and methodology: This research study investigates the genetic and mechanistic pathway by investigating the single-nucleotide polymorphism of apelin and IGF2BP2 genes (i.e., rs2235306 and rs11705701) along with an inflammatory marker, Interleukin-6 (IL-6), and apelin protein levels among obese versus non-obese Mets subjects of the Pakistani population. A cross sectional study was conducted at the Multidisciplinary Laboratory of Aga Khan University (MDLAKU), recruiting subjects by non-probability purposive convenience sampling based on MetS predefined criteria. DNA was extracted from blood samples and genotyped using Tetra-ARMS PCR. Apelin and IL-6 Protein expression in serum was detected by Enzyme-linked immunosorbent assay (ELISA). IL-6 expression was also determined by Western blot analysis.
Results and conclusion: Triglycerides, blood glucose, and apelin levels were elevated in MetS subjects independent of BMI. IL-6 levels remained unchanged. Adjusted logistic model (sex, age) showed a 52% reduction in MetS risk for Apelin SNP (p = 0.028) and 2.5-fold increased risk in AA homozygotes of the IGFBP2 gene (p = 0.006). PCA identified 4 factors with 56% variance linking gender-inflammation, metabolic-age, genotype-fat distribution, and glycemic control. K Means cluster analysis showed insulin (p < 0.022) and apelin (p < 0.001) influenced metabolic variations. A protective effect for rs2235306 and risk for rs11705701 was observed in the study. This study also revealed apelin and insulin as potential biomarkers for diagnosing MetS subject

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1

Last Page

29

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