Investigation of TNF-α and DC-SIGN promoter polymorphisms in patients with dengue fever in Lahore city of Pakistan

Abstract

Background and Objective: Dengue fever (DF) has been a major health concern globally. Pakistan is also combating this infection for the last decade. Cytokine genes play an important role in DF pathogenesis. This study aimed to analyze dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and tumor necrosis factor α (TNF-α) genes promoter polymorphisms in DF patients. Methods: A total of 140 (n = 140) dDF patients were recruited for study at the Department of Human Genetics and Molecular Biology of University of Health Sciences, Lahore, Pakistan over a period of 3 years. Simple DF was noted in 105 patients (75%) while 35 (25%) showed bleeding complications. All patients were found positive for dengue non-structural protein or dengue IgM. All patients were tested for two polymorphisms in TNF-α (-238G/A, and -308G/A) and one polymorphism in DC-SIGN (-336G/A) using restriction fragment length polymorphism technique. A single nucleotide polymorphism stats program was used for statistical analysis. Results: Susceptibility to develop dengue infection in the presence of -336G allele odds ratio (OR = 27.95, p = <0.0001) and GG genotype (OR = 183.77, p = <0.0001) was found to be significantly associated in this study. Presence of a combination of alleles -336G/-238A/-308A was noted in 59.4% of DF cases and 7.6% healthy controls, a difference with statistical significance (OR = 31.46, p = <0.0001). Moreover, prevalence of DF symptoms showed a trend higher in G-carriers versus non-G-carriers of DC-SIGN -336 polymorphism. Conclusion: This work suggests a potential association of DC-SIGN -336 polymorphism with susceptibility to develop symptomatic dengue illness. However, no potential association was found between TNF-α promoter polymorphisms and dengue infection in this study.