Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.
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)-gamma 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 > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma 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.
Wellcome Trust Centre for Research in Clinical Tropical Medicine, Division of Medicine, Imperial College London, London, UK. a.martineau@qmul.ac.uk
A R
AR
Martineau
A C C S
AC
Leandro
S T
ST
Anderson
S M
SM
Newton
K A
KA
Wilkinson
M P
MP
Nicol
S M
SM
Pienaar
K H
KH
Skolimowska
M A
MA
Rocha
V C
VC
Rolla
M
M
Levin
R N
RN
Davidson
S A
SA
Bremner
C J
CJ
Griffiths
B S
BS
Eley
M G
MG
Bonecini-Almeida
R J
RJ
Wilkinson
D000328:Adult; D000483:Alleles; D001208:Asia / Q000208:ethnology; D001938:Brazil; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013019:South Africa; D014376:Tuberculosis / Q000208:ethnology / Q000235:genetics*; D006113:United Kingdom; D014807:Vitamin D / Q000097:blood*; D014809:Vitamin D-Binding Protein / Q000097:blood* / Q000235:genetics*
D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D007371:Interferon-gamma