Association between Gc genotype and susceptibility to TB is dependent on vitamin D status

A. R. Martineau; A. C.C.S. Leandro; S. T. Anderson; S. M. Newton; K. A. Wilkinson; M. P. Nicol; S. M. Pienaar; K. H. Skolimowska; M. A. Rocha; V. C. Rolla; M. Levin; R. N. Davidson; S. A. Bremner; C. J. Griffiths; B. S. Eley; M. G. Bonecini-Almeida; R. J. Wilkinson

doi:10.1183/09031936.00087009

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status

A. R. Martineau, A. C.C.S. Leandro, S. T. Anderson, S. M. Newton, K. A. Wilkinson, M. P. Nicol, S. M. Pienaar, K. H. Skolimowska, M. A. Rocha, V. C. Rolla, M. Levin, R. N. Davidson, S. A. Bremner, C. J. Griffiths, B. S. Eley, M. G. Bonecini-Almeida, R. J. Wilkinson

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Abstract

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-γ release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p=0.009). This association was preserved if serum 25(OH)D was <20 nmol·L^-1 (p=0.01) but not if serum 25(OH)D was ≥20 nmol·L^-1 (p=0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-γ release in Gujarati Asian TB contacts (p=0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied. Copyright

Original language	English
Pages (from-to)	1106-1112
Number of pages	7
Journal	European Respiratory Journal
Volume	35
Issue number	5
DOIs	https://doi.org/10.1183/09031936.00087009
Publication status	Published - 1 May 2010
Externally published	Yes

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Martineau, A. R., Leandro, A. C. C. S., Anderson, S. T., Newton, S. M., Wilkinson, K. A., Nicol, M. P., Pienaar, S. M., Skolimowska, K. H., Rocha, M. A., Rolla, V. C., Levin, M., Davidson, R. N., Bremner, S. A., Griffiths, C. J., Eley, B. S., Bonecini-Almeida, M. G., & Wilkinson, R. J. (2010). Association between Gc genotype and susceptibility to TB is dependent on vitamin D status. European Respiratory Journal, 35(5), 1106-1112. https://doi.org/10.1183/09031936.00087009

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title = "Association between Gc genotype and susceptibility to TB is dependent on vitamin D status",

abstract = "Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-γ release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p=0.009). This association was preserved if serum 25(OH)D was <20 nmol·L-1 (p=0.01) but not if serum 25(OH)D was ≥20 nmol·L-1 (p=0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-γ release in Gujarati Asian TB contacts (p=0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied. Copyright",

keywords = "25-hydroxyvitamin D, Gc genotype, Tuberculosis, Vitamin D binding protein",

author = "Martineau, {A. R.} and Leandro, {A. C.C.S.} and Anderson, {S. T.} and Newton, {S. M.} and Wilkinson, {K. A.} and Nicol, {M. P.} and Pienaar, {S. M.} and Skolimowska, {K. H.} and Rocha, {M. A.} and Rolla, {V. C.} and M. Levin and Davidson, {R. N.} and Bremner, {S. A.} and Griffiths, {C. J.} and Eley, {B. S.} and Bonecini-Almeida, {M. G.} and Wilkinson, {R. J.}",

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Martineau, AR, Leandro, ACCS, Anderson, ST, Newton, SM, Wilkinson, KA, Nicol, MP, Pienaar, SM, Skolimowska, KH, Rocha, MA, Rolla, VC, Levin, M, Davidson, RN, Bremner, SA, Griffiths, CJ, Eley, BS, Bonecini-Almeida, MG & Wilkinson, RJ 2010, 'Association between Gc genotype and susceptibility to TB is dependent on vitamin D status', European Respiratory Journal, vol. 35, no. 5, pp. 1106-1112. https://doi.org/10.1183/09031936.00087009

TY - JOUR

T1 - Association between Gc genotype and susceptibility to TB is dependent on vitamin D status

AU - Martineau, A. R.

AU - Leandro, A. C.C.S.

AU - Anderson, S. T.

AU - Newton, S. M.

AU - Wilkinson, K. A.

AU - Nicol, M. P.

AU - Pienaar, S. M.

AU - Skolimowska, K. H.

AU - Rocha, M. A.

AU - Rolla, V. C.

AU - Levin, M.

AU - Davidson, R. N.

AU - Bremner, S. A.

AU - Griffiths, C. J.

AU - Eley, B. S.

AU - Bonecini-Almeida, M. G.

AU - Wilkinson, R. J.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-γ release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p=0.009). This association was preserved if serum 25(OH)D was <20 nmol·L-1 (p=0.01) but not if serum 25(OH)D was ≥20 nmol·L-1 (p=0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-γ release in Gujarati Asian TB contacts (p=0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied. Copyright

AB - Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-γ release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p=0.009). This association was preserved if serum 25(OH)D was <20 nmol·L-1 (p=0.01) but not if serum 25(OH)D was ≥20 nmol·L-1 (p=0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-γ release in Gujarati Asian TB contacts (p=0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied. Copyright

KW - 25-hydroxyvitamin D

KW - Gc genotype

KW - Tuberculosis

KW - Vitamin D binding protein

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DO - 10.1183/09031936.00087009

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SN - 0903-1936

VL - 35

SP - 1106

EP - 1112

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 5

ER -

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status

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