No associations of human pulmonary tuberculosis with Sp110 variants

Journal of Medical Genetics (Impact Factor: 6.34). 08/2006; 43(7):e32. DOI: 10.1136/jmg.2005.037960
Source: PubMed


After a recent report on the role of the Ipr1 gene in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, the human Ipr1 homologue, Sp110, was considered a promising candidate for an association study in human tuberculosis.
In a sample of >1000 sputum positive, HIV negative West African patients with pulmonary tuberculosis and >1000 exposed, apparently healthy controls, we have genotyped 21 Sp110 gene variants that were either available from public databases, including HapMap data, or identified by DNA re-sequencing.
No significant differences in the frequencies of any of the 21 variants were observed between patients and controls. This applied also for HapMap tagging variants and the corresponding haplotypes, when including sliding window analyses with three adjacent variants, and when stratifying controls for positivity and negativity according to the results of intradermal tuberculin (purified protein derivative, PPD) skin tests. DNA re-sequencing revealed 13 novel Sp110 variants in the 5'-UTR, exons, and adjacent intronic regions.
Based on the results obtained in this case-control study, the hypothesis that Sp110 variants and haplotypes might be associated with distinct phenotypes of human M tuberculosis infection is doubtful.

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Available from: Ellis Owusu-Dabo
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    • "This approach successfully identified multiple susceptibility loci and one gene Ipr1 (mouse) that alters macrophage necrosis and increases susceptibility, and helped to identify SP110 (the human homolog to mouse Ipr1) polymorphisms in TB-infected individuals (Kramnik et al., 1998, 2000; Pan et al., 2005; Tosh et al., 2006; Yan et al., 2006; Kramnik, 2008; Pichugin et al., 2009; Sissons et al., 2009). However, the SP110 polymorphisms do not explain all TB cases (Thye et al., 2006; Png et al., 2012) and additional studies are needed. A mouse model might not recapitulate all characteristics of human pulmonary TB. "
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    • "The study design and the enrollment procedure have been described in detail previously [14,26]. In brief, participants were recruited at the two major Ghanaian teaching hospitals in Accra and Kumasi and at additional hospitals and polyclinics in these metropolitan areas and at regional district hospitals. "
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    • "As in the present study, this coding SNP was not localized to any of the principal domains of the SP110 protein, and the authors did not establish a possible functional effect of this SNP, suggesting possible linkage disequilibrium between this SNP and the real causal variant. In any event, remember that the results reported by Tosh et al. (2006) have not been confirmed in subsequent studies (Thye et al., 2006; Babb et al., 2007; Szeszko et al., 2007). "
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