Molecular Insights into Hypertriglyceridemia-Associated Cardiovascular Disease and Pancreatitis in Pakistan: A Systematic Review

Abstract

Background: Hypertriglyceridemia (HTG), defined as fasting triglyceride levels above 150 mg/dL, is a complex lipid disorder that significantly contributes to the burden of cardiovascular disease (CVD) and acute pancreatitis worldwide. While lifestyle factors, such as poor diet, obesity, and diabetes, play a major role in its development, genetics also have a profound impact on when and how the condition manifests, as well as how patients respond to treatment. In Pakistan, where consanguineous marriages are common and dyslipidemia is on the rise, the genetic landscape of HTG offers unique insights but remains largely unexplored. This review summarizes published research on the genetics of HTG in Pakistan. Methods: We systematically searched PubMed and Google Scholar up to June 2025 for studies on Pakistani individuals reporting genetic data related to triglyceride metabolism, using combinations of HTG-related terms and MeSH headings. Eligible designs included case reports, case–control studies, and family studies. Data were extracted on study characteristics, genetic variants, and clinical associations. Results: Five studies met the inclusion criteria. Variants in APOA5, LPL, GPIHBP1, and CETP were associated with severe or moderate HTG, therapeutic responses, and CVD risk. No studies examined the genetic basis of HTG-associated pancreatitis in Pakistan. Limitations included small sample sizes, restricted gene coverage, and the absence of longitudinal follow-up. Conclusion: Limited evidence links both rare, high-impact and common triglyceride-related variants to HTG and CVD risk in Pakistani populations. There is an urgent need for large-scale genomic studies, especially on pancreatitis genetics, to enable precision-based interventions.