SLC11A1 Polymorphisms and TB Figure 5. Meta-analysis of the association between tuberculosis and SLC11A1 59 (GT)n polymorphism (allele 3 vs. other alleles). c = subgroup of patients who were aboriginal Taiwanese; d = subgroup of patients who were Hans; e = HIV-negative pulmonary TB patients; f = HIV- negative extra-pulmonary tuberculosis patients; CI = confidence interval; OR = odds ratio. doi:10.1371/journal.pone.0015831.g005 shown to confer an increased risk of TB on their carriers from African and Asian, whereas they were not statistically associated with TB in those of European origin. Authors suggested this ethnic-specific observation may explain in part by Africans and Asians have greater susceptibility to TB than those of Europeans. Meanwhile, authors also mentioned that this hypothesis needed to be proved in future research due to the limited number of included publications and subjects. Our present updated meta-analysis, based on 36 eligible studies until September 2010, did not present an ethic-specific effect of SLC11A1 polymorphisms. Three ethnic groups were defined with respect to the distribution of study population in the included studies, e.g. Asians, Africans and Westerns (Europeans and Americans). Statistically significant or marginal associations with TB susceptibility were found for the four studied loci in all of the three ethnic groups. Large number of included articles in the present study makes the evidence stronger to propose a consistent effect of SLC11A1 polymorphisms in different populations. In addition, population-based study has shown to be more powerful for such genetic association analysis. However, only minority of included studies (7 of 36) were conducted as population- based and no substantial different or more pronounced effect was observed as compared to those hospital-based studies. The stratified analyses suggested different study population and study base might partly explain the moderate heterogeneity between studies observed in our analyses. Further sensitivity analyses were performed as well to explore potential origin of the heterogeneity (see Table S4). When restrict to analyses on pulmonary TB or excluding those studies specifically on extra- pulmonary TB, better homogeneity between studies was observed. Nevertheless, the effects of the polymorphisms were not substan- tially influenced by such stratified analyses, which suggested that the role of NRAMP1 in the development of TB might not be disease type specific. Further studies addressing the effect of NRAMP1 on pulmonary TB and extra-pulmonary TB, respec- tively, are warranted to verify this hypothesis. There are some limitations to this systematic review that should be kept in mind. First, the potential confounding effect of age, sex and PLoS ONE | www.plosone.org 6 January 2011 | Volume 6 | Issue 1 | e15831