Association of vitamin D receptor (VDR) gene polymorphism with disease severity among dengue patients

Abstract

Background: Vitamin D receptor (VDR) is coded by VDR gene located on chromosome 12. The present study was undertaken to decipher the effect of vitamin D receptor (VDR) gene polymorphism on dengue disease outcome, as there is a dearth of similar studies in the context of Indian population. Methods and materials: The study was conducted in the Virology Laboratory, Department of Microbiology, Maulana Azad Medical College, New Delhi. We studied 100 cases (suspected dengue patients) and 100 healthy controls over a period of 1 year (January 2014 to December 2014). Revised WHO guidelines (2009) were followed to define and characterize a case of dengue. Peripheral venous samples were collected for diagnosis of dengue (NS1 antigen, IgM and IgG antibody). Genomic DNA was extracted from patients and healthy controls and Restriction Fragment Length Polymorphism was done for detection of VDRL gene polymorphism (start codon rs2228570 and 3′ UTR, rs7975232). Data was analysed using SPSS software (version 17.0). A p value < 0.05 was considered statistically significant. Results: VDR gene polymorphism (rs 2228570 and rs 7975232) was screened in the samples. Genotype C/C, C/T and T/T (rs 2228570) was found in 11 (25.58%), 18 (41.9%) and 14 (32.6%) dengue positive cases and 59%, 25% and 16% healthy controls respectively (p = 0.001, significant). Significant association of the T allele of rs 2228570 polymorphism in a dominant mode of inheritance (C/T + T/T genotype) was seen with severe dengue cases [OR of 3.86 (1.59–9.35), p = 0.002 for C/T and 4.69 (1.79–12.3), p = 0.001 for T/T genotypes]. Genotypes A/A, A/C and C/C (rs 7975232) were found in 34.9%, 55.8%, 9.3% dengue positive cases and 31%, 40%, 29% healthy controls respectively. While comparing the A/A with A/C and C/C genotypes among dengue cases and healthy controls, the OR was estimated to be 1.24 (0.55–2.75, p > 0.05) and 0.28 (0.08–0.96, p < 0.05) respectively. This suggested that C/C genotype of rs7975232 was associated with reduced risk of developing symptomatic dengue (p = 0.035). Conclusion: A significant association of T allele of rs 2228570 polymorphism was found in severe dengue cases in the study. The results also suggest that C/C genotype of rs 7975232 was associated with reduced risk of developing symptomatic dengue.