Association of HLA-DR, -DQ, and Vitamin D Receptor Alleles and Haplotypes with Tuberculosis in the Venda of South Africa

Lombard, Zané; Dalton, Desiré L.; Venter, Philip A.; Williams, Robert C.; Bornman, Liza

doi:10.1016/j.humimm.2006.04.008

Cited by 90 publications

(78 citation statements)

References 33 publications

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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%

“…Curved arrows indicate transcription start sites (TSSs). The position of CGIs are shown above the gene diagram and that of SNPs previously implicated in TB susceptibility below the gene diagram: Cdx2 [13], A1012G [13], FokI, BsmI, ApaI, TaqI [10][11][12]14]. ApaI and TaqI are located in CGI 1060.…”

Section: Discussionmentioning

confidence: 99%

“…For the ethnicity study, DNA from Epstein-Barr Virus (EBV) transformed B-lymphocytes of unrelated individuals (30 CAU from North America, from the HD50CAU panel and 30 YRI from the International HapMap Project) was purchased from Coriell Cell Repositories (Camden, NJ, USA). Considering TB status, DNA samples from 32 pulmonary TB cases and 29 healthy TB contacts (controls) were randomly selected from a study population previously collected in the Venda, Limpopo Province, South Africa [12]. Briefly, pulmonary TB was confirmed by sputum smears, positive for acid-fast bacilli.…”

Section: Subjectsmentioning

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%

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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: Discussionmentioning

confidence: 99%

Section: Subjectsmentioning

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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Virulence and Persistence Mechanisms ofMycobacterium tuberculosis

Boshoff¹,

Singh²,

Barry³

2008

Handbook of Tuberculosis

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Vitamin D Deficiency and Its Health Consequences in Africa

Prentice¹,

Schoenmakers²,

Jones³

et al. 2010

Vitamin D

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Africa is heterogeneous in latitude, geography, climate, food availability, religious and cultural practices, and skin pigmentation. It is expected, therefore, that prevalence of vitamin D deficiency varies widely, in line with influences on skin exposure to UVB sunshine. Furthermore, low calcium intakes and heavy burden of infectious disease common in many countries may increase vitamin D utilization and turnover. Studies of plasma 25OHD concentration indicate a spectrum from clinical deficiency to values at the high end of the physiological range; however, data are limited. Representative studies of status in different countries, using comparable analytical techniques, and of relationships between vitamin D status and risk of infectious and chronic diseases relevant to the African context are needed. Public health measures to secure vitamin D adequacy cannot encompass the whole continent and need to be developed locally.

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Association of HLA-DR, -DQ, and Vitamin D Receptor Alleles and Haplotypes with Tuberculosis in the Venda of South Africa

Cited by 90 publications

References 33 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

Virulence and Persistence Mechanisms ofMycobacterium tuberculosis

Vitamin D Deficiency and Its Health Consequences in Africa

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