| Summary: | <p>Abstract</p> <p>Background</p> <p><it>SLC11A1 </it>has pleiotropic effects on macrophage function and remains a strong candidate for infectious disease susceptibility. 5' and/or 3' polymorphisms have been associated with tuberculosis, leprosy, and visceral leishmaniasis (VL). Most studies undertaken to date were under-powered, and none has been replicated within a population. Association with tuberculosis has replicated variably across populations. Here we investigate <it>SLC11A1 </it>and VL in India.</p> <p>Methods</p> <p>Nine polymorphisms (rs34448891, rs7573065, rs2276631, rs3731865, rs17221959, rs2279015, rs17235409, rs17235416, rs17229009) that tag linkage disequilibrium blocks across <it>SLC11A1 </it>were genotyped in primary family-based (313 cases; 176 families) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between <it>SLC11A1 </it>variants and VL. Quantitative RT/PCR was used to compare SLC11A1 expression in mRNA from paired splenic aspirates taken before and after treatment from 24 VL patients carrying different genotypes at the functional promoter GT<sub>n </sub>polymorphism (rs34448891).</p> <p>Results</p> <p>No associations were observed between VL and polymorphisms at <it>SLC11A1 </it>that were either robust to correction for multiple testing or replicated across primary and replication samples. No differences in expression of SLC11A1 were observed when comparing pre- and post-treatment samples, or between individuals carrying different genotypes at the GT<sub>n </sub>repeat.</p> <p>Conclusions</p> <p>This is the first well-powered study of <it>SLC11A1 </it>as a candidate for VL, which we conclude does not have a major role in regulating VL susceptibility in India.</p>
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