Association analysis of HLA-class II and class III gene polymorphisms in the susceptibility to mediterranean visceral leishmaniasis.
HLA-DRB1, -DQB1, TNFalpha, TNFbeta, HSP70-2 and HSP70-hom genetic polymorphisms were analyzed in 156 unrelated patients who developed mediterranean visceral leishmaniasis (MVL) due to Leishmania infantum, and 154 unrelated healthy controls, who have got asymptomatic infection with this parasite and were selected on the basis of a positive leishmanin skin test (LST). A significantly reduced frequency of HLA-DR2 was observed among MVL patients (16.1%), compared with controls (26.3%) (relative risk = 0.54; p = 0.04). HLA-DR2/DR13 as well as HLA-DQB1*0201/- genotype frequencies were significantly lower in patients vs controls (relapse rate = 0.17 and 0.46, respectively; p < 0.05). However, using Bonferroni correction, none of these associations remained significant. No association was found, between either the -308 base pair TNFalpha gene polymorphism or the NcoI polymorphism in the first intron of the TNFbeta gene and susceptibility to MVL. Analysis of PstI and NcoI polymorphisms in the coding region of HSP70-2 and HSP70-hom genes, respectively, revealed a significantly higher frequency of homozygotes for the HSP70-2/PstI negative allele, among patients (21.8%) vs controls (12.6%) (relapse rate = 1.94; p = 0.04). Again, this result was not significant after using Bonferroni correction. These results do not support association between susceptibility to MVL and the MHC class II and class III loci analyzed in this study.
Meddeb-Garnaoui
A
A
Laboratory of Immunology, Institut Pasteur de Tunis, Tunis-Belvédère, Tunisia. amel.garnaoui@pasteur.rns.tn
Gritli
S
S
Garbouj
S
S
Ben Fadhel
M
M
El Kares
R
R
Mansour
L
L
Kaabi
B
B
Chouchane
L
L
Ben Salah
A
A
Dellagi
K
K
D000818:Animals; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018314:Leishmania infantum; D007898:Leishmaniasis, Visceral / Q000235:genetics* / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics*; D019083:Mediterranean Region; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018840:HSP70 Heat-Shock Proteins; C091879:HSPA2 protein, human; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha