Association of Taq I, Fok I and Apa I polymorphisms in Vitamin D Receptor (VDR) gene with leprosy

Neela, Venkata Sanjeev Kumar; Suryadevara, Naveen Chandra; Shinde, Vidya Gouri; Pydi, Satya Sudheer; Jain, Suman; Jonnalagada, Subbanna; Singh, Surya S.; Valluri, Vijaya Lakshmi; Anandaraj, M.P.J.S.

doi:10.1016/j.humimm.2015.04.002

Cited by 30 publications

(39 citation statements)

References 29 publications

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“…VDR rs2228570 has been evaluated also in leprosy, an infectious disease caused by another species of Mycobacterium . In this case, homozygosity of rs2228570*A was associated with a higher risk to develop leprosy in an Indian population 40 .…”

Section: Discussionmentioning

confidence: 61%

Evaluation of VDR gene polymorphisms in Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

Rodríguez

Carmona

González

et al. 2016

Sci Rep

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Vitamin D is an important modulator of the immune response. It acts over several immune cell types where the Vitamin D receptor (VDR) is expressed. Due to the high relevance of this signaling pathway, several studies have investigated the possible influence of genes involved in the metabolism of Vitamin D and its receptor in different human diseases. Here, we analyzed whether four single-nucleotide polymorphisms of the VDR gene (rs731236, rs7975232, rs1544410 and rs2228570) are involved in the susceptibility to infection by Trypanosoma cruzi and/or to chronic Chagas cardiomyopathy (CCC) in a Colombian endemic population for this parasite. Our results showed that the rs2228570*A allele is associated with CCC development (P = 4.46E−03, OR = 1.51). In summary, the data presented in this report suggest that variation within the VDR gene may affect the immune response against T. cruzi, increasing the probability of cardiac complications in infected individuals.

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Section: Discussionmentioning

confidence: 61%

Evaluation of VDR gene polymorphisms in Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

Rodríguez

Carmona

González

et al. 2016

Sci Rep

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“… 10 Indeed, VDR polymorphism may influence susceptibility to infectious diseases, such as hepatitis B virus infection 62 and leprosy. 63 With respect to Fok I polymorphisms, the short 424 amino acid VDR protein variant (corresponding with the C-allele or “big F” allele) has been found to be more active than the long 427 ff variant. 59 Hence, the f allele of Fok I might decrease the activity of the VDR protein, and then block the binding of active vitamin D and VDR.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis

et al. 2015

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The association between vitamin D receptor (VDR) FokI polymorphism and tuberculosis (TB) risk remains a matter of debate. Potential selection bias exists in most studies using HIV-positive TB patients.An update meta-analysis was carried out to derive a more reliable assessment of the association between FokI polymorphisms and TB risk, especially in HIV-negative TB patients. All major databases from inception to June 2015 were searched for all publications that studied the association between FokI polymorphism and TB risk. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated according to the frequencies of genotypes.In total, 32 studies with 4894 cases and 5319 controls were included in this meta-analysis. In the overall analysis, the estimated OR was 1.34 (95% CI=1.091–1.646, P = 0.005) in the best genetic model (recessive model, ff vs fF+FF) with moderate heterogeneity (I2 = 32.2%, P = 0.043). In the subgroup analysis stratified by HIV status, significant associations were found only in the HIV-negative TB group (OR = 1.60, 95% CI = 1.180–2.077, P = 0.002; I2 = 29.5%, and P = 0.141 for heterogeneity). In the subgroup analysis stratified by ethnicity, significant associations were found in the Asian group (OR = 1.65, 95% CI = 1.205–2.261, P = 0.002; I2 = 43.9%, and P = 0.024 for heterogeneity), but not in the Caucasian group (OR = 1.09, 95% CI = 0.762–1.547, P = 0.649; I2 = 0.0%, and P = 0.740 for heterogeneity) and African group (OR = 0.99, 95% CI = 0.726–1.341, P = 0.934; I2 = 43.9%, and P = 0.024 for heterogeneity).This meta-analysis confirms that VDR FokI polymorphism contributes to the risk of TB, especially in HIV-negative TB patients and in the Asian group. Further studies are required to clarify the role of the FokI polymorphism in HIV-positive TB and in other ethnic groups.

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“…Other associations have only been found once, and the implication of the tested genes in leprosy pathogenesis must be considered with caution: IFNγ and HLA-G in Brazil [ 63 , 64 ]; TLR4 and leukotriene A4 hydrolase ( LTA4H ) in Ethiopia [ 65 , 66 ]; vitamin D receptor ( VDR) [ 67 , 68 ], killer cell immunoglobulin like receptor, two Ig domains and short cytoplasmic tail 3 ( KIR2DS3 ) [ 69 ], heat shock protein 1A ( HSPA1A ), and IL-23R in India [ 70 , 71 ]; lymphotoxin-α ( LTA ) in Malawi [ 53 ]; complement fraction 4 ( C4A ) in Thailand [ 72 ]; IL-12B in Mexico [ 73 ]; IL-12RB2 in Japan [ 74 ]; natural resistance-associated macrophage protein 1 ( NRAMP1 ) in Mali [ 75 ]; laminin 2 ( LAMA2 ) in Indonesia [ 76 ]; defensin-β1 ( DEFB1 ) in Mexico [ 77 ]; and optic atrophy 1 ( OPA1 ) in China [ 78 ]. Interestingly, for VDR, one study identified a polymorphism associated with leprosy when comparing MB to PB [ 67 ], while a second study identified a haplotype when comparing MB to controls and another haplotype when comparing PB to controls [ 68 ]. Finally, a Brazilian study illustrated the impact of clinical classification.…”

Section: Human Genetics Of Leprosy Subtypesmentioning

confidence: 99%

Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases

et al. 2016

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After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This “polarization” of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes.Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy.

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Association of Taq I, Fok I and Apa I polymorphisms in Vitamin D Receptor (VDR) gene with leprosy

Cited by 30 publications

References 29 publications

Evaluation of VDR gene polymorphisms in Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

Evaluation of VDR gene polymorphisms in Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

Vitamin D Receptor Gene FokI Polymorphism Contributes to Increasing the Risk of Tuberculosis

Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases

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