VDR polymorphism, gene expression and vitamin D levels in leprosy patients from North Indian population

Abstract

BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae and mainly affects skin, peripheral nerves. Vitamin D receptor (VDR) gene polymorphism has been found to be associated with leprosy. Vitamin D has been shown to control several host immunomodulating properties through VDR gene. Vitamin D deficiency was also found to be linked to an increased risk for several infections and metabolic diseases.ObjectiveIn the present study, we investigated the association of VDR gene polymorphism, mRNA gene expression of VDR and the vitamin D levels with leprosy and its reactional states.MethodologyA total of 305 leprosy patients consisting of tuberculoid (TT), borderline tuberculoid (BT), borderline lepromatous (BL), lepromatous leprosy (LL), as well as 200 healthy controls were enrolled in the study. We identified single nucleotide polymorphisms (SNPs) of VDR Taq1, Fok1 and Apa1, as well as the expression of VDR mRNA gene using PCR-based restriction fragment length polymorphism (RFLP) analysis and real-time PCR respectively. We also performed ELISA to measure vitamin D levels.ResultWe observed that SNP of VDR gene (Fok1 and Taq1) are associated with the leprosy disease. The allelic frequency distribution of T and t allele (p = 0.0037), F and f allele (p = 0.0024) was significantly higher in leprosy patients and healthy controls. ff genotype of Fok1 was found to be associated with leprosy patients [p = 0.0004; OR (95% CI) 3.148 (1.662–5.965)]. The recessive model of Fok1 genotype was also found to be significantly associated in leprosy patients in comparison to healthy controls [p = 0.00004; OR (95% CI) 2.85 (1.56–5.22)]. Leprosy patients are significantly associated with t-F-a haplotype. Further, VDR gene expression was found to be lower in non-reaction group compared to that of reaction group of leprosy and healthy controls. Paradoxically, we noted no difference in the levels of vitamin D between leprosy patients and healthy controls.ConclusionBlood levels of vitamin D do not play any role in clinical manifestations of any forms of leprosy. ff genotype of Fok1 and tt genotype of Taq1 was found to be associated with leprosy per se. Association of t-F-a haplotype with leprosy was found to be significant and could be used as a genetic marker to identify individuals at high risk for developing leprosy. VDR gene expression was lower in TT/BT and BL/LL groups of leprosy in comparison to that of healthy controls.

Association of Fok1 VDR polymorphism with Vitamin D and its associated molecules in pulmonary tuberculosis patients and their household contacts

“…The findings are in concordance with one of the study in Chinese Han population showing association of ‘ff’ genotype with susceptibility to TB 9 . Similar findings were observed in a north Indian population showing significant association of Fok1 VDR polymorphism with leprosy 16 . However, in other studies from Egypt and India, no significant association was observed for VDR Fok1 polymorphism with susceptibility to TB 10,17 .…”

Lower levels of vitamin D are associated with SARS-CoV-2 infection and mortality in the Indian population: An observational study

“… State/ union territories Case/million Death/million Total no. of healthy subjects Mean 25(OH)D levels (ng/ml) References Andhra Pradesh 5530 50 1936 18 [32] , [33] , [34] , [35] , [36] Assam 2390 6 768 26 [37] , [38] , [39] Bihar 940 4 50 30 [40] Chandigarh 1830 27 878 34 [41] , [42] , [43] , [44] , [45] , [46] Delhi 8970 249 2919 15 [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] Goa 7520 64 …”

Vitamin D Receptor Gene Polymorphisms Are Associated With Leprosy in Southern Brazil

“…Low levels of expression, VDR stability and vitamin D3-VDR interaction were related to leprosy and its complications (44). It has been shown that some individuals with normal levels of vitamin D3, but with low levels of VDR protein, had a high bacilloscopic index and type 2 reaction (45).…”