Association of Intercellular Adhesion Molecule 1 (ICAM-1) (rs5498) genetic polymorphism and dengue In Sabah East Malaysia population

Background Dengue remains a significant public health challenge in Malaysia, particularly in Sabah where indigenous populations such as the Kadazan-Dusun and Bajau are highly affected. Host genetic factors, including polymorphisms in immune-related genes, may influence individual susceptibility to dengue infection. This study investigates the association between Intercellular Adhesion Molecule-1 (ICAM-1) rs5498 (K469E) polymorphism and dengue infection in the Sabahan population, with a focus on ethnic and gender stratification. Methods A total of 382 participants were recruited, comprising 191 laboratory-confirmed dengue cases and 191 healthy controls, stratified by ethnicity (Kadazan-Dusun, Bajau) and gender. Genotyping of ICAM-1 rs5498 was performed using a Fluidigm Genotyping Array. Genotype and allele frequencies were compared using chi-square tests. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate associations under various genetic models. Results The GG genotype and G allele of ICAM-1 rs5498 were significantly more frequent among dengue cases compared to controls (GG: 53.9% vs. 25.7%; G allele: 64.4% vs. 40.3%; p  < 0.001). The GG genotype was associated with increased risk of dengue in both Kadazan-Dusun (OR = 3.46, 95% CI: 1.996–6.008) and Bajau (OR = 4.36, 95% CI: 1.414–13.465) ethnicities. Gender-stratified analysis revealed a stronger association among females (OR = 4.18, 95% CI: 2.072–8.410; p  < 0.001). Subgroup analysis further supported these findings, with significant risk observed in Kadazan-Dusun and Bajau females. Conclusion The ICAM-1 rs5498 GG genotype and G allele are significantly associated with increased susceptibility to dengue infection in the Sabahan population, particularly among females. These findings highlight the potential role of ICAM-1 as a genetic biomarker for dengue risk and underscore the importance of considering ethnic and gender differences in genetic epidemiology studies of infectious diseases.