Home Economics American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research
Focusing on the MHC class III region
Two of the most widely investigated loci in the context of susceptibility to infectious disease are TNF and LTA within the MHC class III region. Indeed there is well known LD between these two loci. Studies of class III loci and susceptibility to CD, mostly on ethnically mixed populations from Brazil, are summarized in Table 27.2. All studies, bar one, address at a minimum susceptibility to CCC. The variation examined is SNPs except for TNF where three Brazilian studies utilize microsatellite markers.42-44 Whereas the TNF-308 polymorphism is widely used, and has a literature debating its functional relevance, it has the major problem of being uninformative, with a MAF of <0.1 in many populations. This together with the small sample sizes of some studies means that a failure to detect association may merely reflect lack of information. The highly polymorphic microsatellites provide much greater information than SNPs, although integrating SNP-based and microsatellite-based findings is not always straightforward.
For TNF, associations were reported at positions -1031 in Colombia,39 -308 in Colombia and Mexico,39,41 -238 in Brazil,40 and for microsatellite markers in Brazil.44 However others reported no association at positions -308 in Brazil,38,40,43 -238 in Mexico,41 and for microsatellite markers in Brazil.43 Only a minority of studies considered LD and haplotypes.39,44 There is insufficient data, even for TNF-308, for conclusive meta-analysis. LTA+252*G and the LTA+80*C+252*G haplotype were associated with CCC in Brazilian populations,46,47 although LTA+252 was not associated in a small Peruvian study.45 Some of these studies have attempted to correlate expression/production of TNF-a with polymorphisms,40,46,47 and one study with survival.42 TNF-238*A carriers had high levels of TNF-a,40 whereas LTA+ 80*A homozygotes produced low levels.46
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