Association between Gc genotype and susceptibility to TB is dependent on vitamin D status
1106 - 1112
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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.
AuthorsMartineau, 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
- College Publications