Analysis of the 5q31-q33 locus shows an association between IL13-1055C/T IL-13-591A/G polymorphisms and Schistosoma haematobium infections.
Millions of humans are exposed to schistosome infections, which cause severe kidney and liver disease and 280,000 deaths annually. Th2-mediated immunity is critical to human defenses against this pathogen and susceptibility to infection is controlled by a major genetic locus that includes IL4, IL5, and IL13 genes. These observations led us to evaluate whether certain polymorphisms in IL4, IL5, or IL13 determine schistosome infection. The study was performed in two Dogon villages where Schistosoma haematobium is endemic. Schistosome infections were evaluated by counting eggs and measuring worm Ags in urine. Genetic polymorphisms were determined by restriction enzyme analysis or by primer extension and denaturing high-performance liquid chromatography analysis. Associations were tested using family-based association tests and logistical regression analysis. The alleles IL13-1055C (p = 0.05) and IL13-591A (p = 0.01) are shown, by family-based association test, to be preferentially transmitted to children with the 10% highest infections. A logistic regression analysis that included IL13-1055 G/G, G/T and T/T genotypes, age, gender, and village of residency, applied to the whole study population, showed that subjects bearing the IL13-1055T/T genotype were on average much less infected than individuals with other genotypes. Previous studies on asthma indicated that the IL13-1055T allele increased gene transcription, which is in agreement with the fact that this cytokine enhances resistance to infection by schistosome in humans.
Kouriba
Bourema
B
Department of Epidemiology and Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, and Service of Internal Medicine, National Hospital of Point G, Bamako, Mali.
Chevillard
Christophe
C
Bream
Jay H
JH
Argiro
Laurent
L
Dessein
Helia
H
Arnaud
Violaine
V
Sangare
Lansana
L
Dabo
Abdoulaye
A
Beavogui
Abdou Habib
AH
Arama
Charles
C
Traoré
Hamar A
HA
Doumbo
Ogobara
O
Dessein
Alain
A
D000225:Adenine; D000328:Adult; D000818:Animals; D000947:Antigens, Helminth / Q000096:biosynthesis / Q000378:metabolism; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003596:Cytosine; D005819:Genetic Markers; D005838:Genotype; D006147:Guanine; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics; D015999:Multivariate Analysis; D009679:Nuclear Family; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012553:Schistosomiasis haematobia / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology; D013941:Thymine
D000947:Antigens, Helminth; D005819:Genetic Markers; D018793:Interleukin-13; D015848:Interleukin-5; D009687:Nuclear Proteins; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine