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.
Martineau
A R
AR
Wellcome Trust Centre for Research in Clinical Tropical Medicine, Division of Medicine, Imperial College London, London, UK. a.martineau@qmul.ac.uk
Leandro
A C C S
AC
Anderson
S T
ST
Newton
S M
SM
Wilkinson
K A
KA
Nicol
M P
MP
Pienaar
S M
SM
Skolimowska
K H
KH
Rocha
M A
MA
Rolla
V C
VC
Levin
M
M
Davidson
R N
RN
Bremner
S A
SA
Griffiths
C J
CJ
Eley
B S
BS
Bonecini-Almeida
M G
MG
Wilkinson
R J
RJ
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