Analysis of the 5q31 33 locus shows an association between single nucleotide polymorphism variants in the IL-5 gene and symptomatic infection with the human blood fluke, Schistosoma japonicum.
Genetic studies of human susceptibility to Schistosoma (blood fluke) infections have previously identified a genetic locus determining infection intensity with the African species, Schistosoma mansoni, in the 5q31-33 region of the human genome that is known to contain the Th2 immune response cluster, including the genes encoding the IL-4, IL-5, and IL-13 cytokines. These cytokines are key players in inflammatory immune responses and have previously been implicated in human susceptibility to infection with the Asian species, S. japonicum. In a nested case control study, we genotyped 30 HapMap tagging single nucleotide polymorphisms (SNPs) across these three genes in 159 individuals identified as putatively susceptible to reinfection with S. japonicum and in 133 putatively resistant individuals. A third group comprising 113 individuals demonstrating symptomatic infection was also included. The results provided no significant association at a global level between reinfection predisposition and any of the individual SNPs or haplotype blocks. However, two tagging SNPs in IL-5 demonstrated globally significant association with susceptibility to symptomatic infection. They were in strong linkage disequilibrium with each other and were found to belong to the same haplotype block that also provided a significant association after permutation testing. This haplotype was located in the 3'-untranslated region of IL-5, suggesting that variants in this region of IL-5 may modulate the immune response in these individuals with symptomatic infection.
Molecular Parasitology Laboratory, Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research and University of Queensland, Australia. Magda.Ellis@qimr.edu.au
Magda K
MK
Ellis
Zhen Zhen
ZZ
Zhao
Hong-Gen
HG
Chen
Grant W
GW
Montgomery
Yue-Sheng
YS
Li
Donald P
DP
McManus
D020413:3' Untranslated Regions / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012554:Schistosomiasis japonica / Q000235:genetics* / Q000276:immunology*
D020413:3' Untranslated Regions; D015848:Interleukin-5