Tuberculosis and Chronic Hepatitis B Virus Infection in Africans and Variation in the Vitamin D Receptor Gene

Bellamy, Richard; Ruwende, Cyril; Corrah, Tumani; McAdam, Keith P. W. J.; Thursz, Mark; Whittle, Hilton; Hill, Adrian V. S.

doi:10.1086/314614

Cited by 385 publications

(288 citation statements)

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“…Furthermore, it harboured the SNPs ApaI in intron 8 and TaqI in exon 9 (Fig. 1B), both previously implicated in TB susceptibility [10][11][12][13][14]. TaqI and rs4987032 (immediately upstream of TaqI in exon 9) could directly affect methylation due to their respective location in CpGs 5 and 6 of CGI 1060.…”

Section: Discussionmentioning

confidence: 91%

“…From a genetic perspective, it is still uncertain whether TaqI or a linked marker is associated with TB. For example, the tt genotype, which is often associated with lower bone mineral density, was found less frequently in patients with pulmonary TB in The Gambia [10] but was not confirmed in a subsequent West African study that supported VDR haplotype association [11], similar to a South African study [12]. A study in India showed the tt genotype to be associated with TB [14].…”

Section: Discussionmentioning

confidence: 99%

“…Vitamin D restricts Mycobacterium tuberculosis (M. tuberculosis) growth in macrophages through the production of the anti-microbial peptide, cathelicidin [9]. Genetic variation in VDR has been associated with TB [10][11][12][13][14] but the role of epigenetic variation involving VDR, in differential TB susceptibility has, to our knowledge, not yet been reported. The consideration of VDR methylation as a possible factor contributing to disease predisposition, particularly TB, is motivated by previous studies showing that the VDR is indeed epigenetically regulated in certain diseases or conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Identifying VDR methylation as an additional factor contributing to disease susceptibility may also minimise inconsistent VDR-disease associations often observed among populations and for traits ranging from bone mass density and diabetes [4] to TB [20] where the association with TaqI (T/t or nucleotides T/C) in particular has generated controversy [10,11]. Rather than studying genetic variants in isolation, the common disease genetic epigenetic (CDGE) hypothesis encourages the simultaneous analysis of both genetic and epigenetic variants (MVPs) to construct 'hepitypes' in order to increase the power of associations in epidemiological studies and minimise inconsistent associations [18,21].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism

et al. 2011

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The Vitamin D Receptor (VDR) gene encodes a transcription factor which, on activation by vitamin D, modulates diverse biological processes including calcium homeostasis and immune function. Genetic variation involving VDR shows striking differences in allele frequency between populations and has been associated with disease susceptibility including tuberculosis and autoimmunity, although results have often been conflicting. We hypothesized that methylation of VDR may be population specific and that the combination of differential methylation and genetic variation may characterise TB predisposition. We use bisulphite conversion and/or pyrosequencing to analyse the methylation status of 17 CpGs of VDR and to genotype 7 SNPs in the 3′ CpG Island (CGI 1060), including the commonly studied SNPs ApaI (rs7975232) and TaqI (rs731236). We show that for lymphoblastoid cell lines from two ethnically diverse populations (Yoruba from HapMap, n=30 and Caucasians, n=30) together with TB cases (n=32) and controls (n=29) from the Venda population of South Africa there are methylation variable positions (MVPs) in the 3′ end that significantly distinguish ethnicity (9/17 CpGs) and TB status (3/17 CpGs). Moreover methylation status shows complex association with TaqI genotype highlighting the need to consider both genetic and epigenetic variants in genetic studies of VDR association with disease.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism

et al. 2011

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“…The genetic analysis of a complex trait such as susceptibility to tuberculosis is extremely difficult in humans due to variable pathogenicity determinants of the bacterium, unequal exposure, incomplete penetrance, phenocopies, locus heterogeneity, and polygenic effects. 4 Case-control studies in endemic areas of tuberculosis using candidate genes have revealed association of susceptibility to disease with alleles of genes encoding the macrophage natural resistance protein NRAMP1, 9 the vitamin D receptor, 10 and HLA-DQ 11 in specific populations. However, the overall effect of these genes is acknowledged to be small, and other genes are certain to play a role in susceptibility to human tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

Genetic control of susceptibility to infection with Mycobacterium tuberculosis in mice

Fortin

et al. 2000

Genes Immun

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Molecular and immunogenetic analysis of major histocompatibility haplotypes in northern bobwhite enable direct identification of corresponding haplotypes in an endangered subspecies, the masked bobwhite

et al. 1999

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The major histocompatibility complex (MHC) is a group of genetic loci coding for haplotypes that have been associated with fitness traits in mammals and birds. Such associations suggest that MHC diversity may be an indicator of overall genetic fitness of endangered or threatened species. The MHC haplotypes of a captive population of 12 families of northern bobwhites (Colinus virginianus) were identified using a combination of immunogenetic and molecular techniques. Alloantisera were produced within families of northern bobwhites and were then tested for differential agglutination of erythrocytes of all members of each family. The pattern of reactions determined from testing these alloantisera identified a single genetic system of alloantigens in the northern bobwhites, resulting in the assignment of a tentative genotype to each individual within the quail families. Restriction fragment patterns of the DNA of each bird were determined using the chicken MHC B‐G cDNA probe bg11. The concordance between the restriction fragment patterns and the alloantisera reactions showed that the alloantisera had identified the MHC of the northern bobwhite and supported the tentative genotype assignments, identifying at least 12 northern bobwhite MHC haplotypes. Eighteen northern bobwhite alloantisera were then used to detect a minimum of 17 masked bobwhite MHC haplotypes. Subsequent restriction fragment pattern analyses using cDNA probes for chicken MHC genes were in agreement with agglutination patterns displayed by the antisera, showing that the immunogenetically identified alloantigen system constituted the MHC of the masked bobwhite. These data demonstrate that a non‐endangered species may be used to provide antisera for differentiating MHC haplotypes in a closely related endangered species, thus providing a practical basis for long‐range monitoring of MHC haplotypes of birds surviving in their native habitats. Zoo Biol 18:279–294, 1999. © 1999 Wiley‐Liss, Inc.

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Tuberculosis and Chronic Hepatitis B Virus Infection in Africans and Variation in the Vitamin D Receptor Gene

Cited by 385 publications

References 14 publications

Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism

Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism

Genetic control of susceptibility to infection with Mycobacterium tuberculosis in mice

Molecular and immunogenetic analysis of major histocompatibility haplotypes in northern bobwhite enable direct identification of corresponding haplotypes in an endangered subspecies, the masked bobwhite

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