RT Journal Article
SR Electronic
T1 Association between Gc genotype and susceptibility to TB is dependent on vitamin D status
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1106
OP 1112
DO 10.1183/09031936.00087009
VO 35
IS 5
A1 A. R. Martineau
A1 A. C. C. S. Leandro
A1 S. T. Anderson
A1 S. M. Newton
A1 K. A. Wilkinson
A1 M. P. Nicol
A1 S. M. Pienaar
A1 K. H. Skolimowska
A1 M. A. Rocha
A1 V. C. Rolla
A1 M. Levin
A1 R. N. Davidson
A1 S. A. Bremner
A1 C. J. Griffiths
A1 B. S. Eley
A1 M. G. Bonecini-Almeida
A1 R. J. Wilkinson
YR 2010
UL http://erj.ersjournals.com/content/35/5/1106.abstract
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.