This variant, formerly titled MYCOBACTERIUM TUBERCULOSIS, SUSCEPTIBILITY TO (see 607948), has been reclassified based on the findings of Thye et al. (2006) and Szeszko et al. (2007).
Tosh et al. (2006) examined 27 SNPs in the SP110 gene in 219 Gambian families and identified 3 that were associated with tuberculosis, including T/C in intron 6 (rs2114592). The most common allele (T) was transmitted more often than expected to affected offspring. Examination of an additional 99 Guinean and 102 Guinea-Bissau families independently replicated the association. The SNP did not affect a known functional domain of SP110.
Thye et al. (2006) observed no significant differences in the frequencies of 21 SP110 variants, including leu425 to ser (604457.0003), between 2,004 sputum-positive, HIV-negative Ghanaian tuberculosis patients and 1,231 exposed, healthy personal contacts and 1,135 community controls. They concluded that an association of SP110 variants and distinct phenotypes of human M. tuberculosis infection is doubtful.
Szeszko et al. (2007) genotyped 29 SNPs in SP110, including 7 causing amino acid changes, and 15 ancestry-informative markers as genomic controls in nearly 2,000 HIV-seronegative, M. tuberculosis culture-positive Russians and a similar number of controls. They found no evidence for association of SP11O SNPs, including leu425 to ser, with susceptibility to adult pulmonary tuberculosis. Szeszko et al. (2007) proposed that the effect of SP110 polymorphisms in outbred human populations may be smaller than the effect of Ipr1 in inbred mice and emphasized the importance of whole-genome scans to identify genes and causal variants predisposing to tuberculosis in human populations.
