Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy.
We have determined IL-10 promoter genotypes of five single-nucleotide polymorphisms (SNPs): T-3575A, A-2849G, C-2763A, -A-1082G and C-819T. The haplotype frequencies were defined in healthy subjects compared to leprosy patients, and analyzed for their occurrence in multi- (MB) vs paucibacillary (PB) as severe and mild forms of leprosy, respectively. Haplotypes defined by three SNP positions (-3575, -2849 and -2763) captured significant differences between controls and patients (P=0.04). The haplotype carrying -3575A, -2849G and -2763C was associated with resistance to leprosy and to the development of severe forms of the disease using either a binomial (controls vs cases, P=0.005, OR=0.35, CI=0.13-0.91) or ordinal (controls vs PB vs MB, P=0.006, OR=0.32, CI=0.12-0.83) model. By contrast, the IL-10 haplotype -3575T/-2849A/-2763C was found to be associated with susceptibility to leprosy per se (P=0.027, OR=2.37, CI=1.04-5.39), but not leprosy type. The data suggest that the IL-10 locus contributes to the outcome of leprosy.
Leprosy Laboratory, Department of Tropical Medicine, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil. mmoraes@fiocruz.br
M O
MO
Moraes
A G
AG
Pacheco
J J M
JJ
Schonkeren
P R
PR
Vanderborght
J A C
JA
Nery
A R
AR
Santos
M E
ME
Moraes
J R
JR
Moraes
T H M
TH
Ottenhoff
E P
EP
Sampaio
T W J
TW
Huizinga
E N
EN
Sarno
D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007918:Leprosy / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D005819:Genetic Markers; D016753:Interleukin-10