Association of vitamin D receptor gene polymorphisms with clinical outcomes of dengue virus infection

Abstract

Vitamin D is known to affect pathogenesis of dengue through modulation of immune responses. Vitamin D exerts its effects through vitamin D receptor (VDR). The functioning of VDR is affected by the gene polymorphisms in the coding (rs2228570) and 3'untranslated region (UTR) (rs1544410, rs7975232 and rs731236). In the present study, VDR gene polymorphisms were investigated in 112 dengue infected patients (83 dengue fever (DF) and 29 dengue hemorrhagic fever cases (DHF)) and 105 apparently healthy controls (HCs) using polymerase chain reaction based restriction fragment length polymorphisms methods. HCs had no documented evidence of symptomatic dengue. Results revealed significantly lower frequency of 'C' allele of rs7975232 in all dengue patients (DEN) as compared to HCs [(P corrected (Pc)=0.014, Odds ratio (OR) 0.51]. The frequency of C/C genotype of rs7975232 was significantly lower in DEN and DF cases compared to HCs (DEN vs. HCs: Pc=0.0184, OR 0.24; DF cases vs. HCs: Pc=0.028, OR 0.21). The frequency of T allele of rs2228570 in a dominant mode was significantly higher in DHF cases as compared to DF cases (P=0.034 OR 2.58). A significantly lower frequency of the haplotype G-C-T (Pc=0.0135) and higher frequency of the haplotype G-A-T (Pc=0.000085) was observed in DEN and DF cases as compared to HCs. The results suggest that the 3'UTR haplotypes of VDR gene are differentially associated with risk of symptomatic dengue requiring hospitalization. The 'T' allele of rs2228570 polymorphism in a dominant mode of inheritance is associated with DHF.