Association of intercellular adhesion molecule 1 (ICAM-1) (rs5498) genetic polymorphism and dengue in Sabah East Malaysia population

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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 83 participants were recruited, comprising 55 laboratory-confirmed dengue cases and 28 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 were significantly more frequent among dengue cases compared with controls (GG: 56.4% vs. 17.9%; G allele: 64.6% vs. 35.7%; p < 0.01). Subgroup analysis revealed significant associations in both Kadazan-Dusun (p = 0.017) and Bajau (p = 0.015) participants, with the A allele conferring a protective effect (overall OR = 0.31, 95% CI: 0.16-0.60). Gender-stratified analysis showed stronger associations in females, where the GG genotype (68.2% vs. 9.1%) and G allele (70.5% vs. 22.7%) were significantly enriched among cases (p ≤ 0.003). Logistic regression under a recessive model confirmed the protective role of the A allele (adjusted OR = 0.19, 95% CI: 0.06-0.59). 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.

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