02436nas a2200481   4500000000100000008004100001260001600042653001500058653001000073653003900083653000900122653002500131653001100156653001900167653003800186653001000224653001700234653001100251653001200262653002400274653000900298653002700307653001600334653003600350653001400386653002900400653001100429653001600440100001300456700001200469700001600481700001300497700001600510700001400526700001200540700001800552700001600570245011700586300000700703490000700710520122300717022001401940       2009                            d  c2009 Jul 1410aAdolescent10aAdult10aAfrican Continental Ancestry Group10aAged10aCase-Control Studies10aFemale10aGene Frequency10aGenetic Predisposition to Disease10aGhana10aHeterozygote10aHumans10aleprosy10aMalaria, Falciparum10aMale10aMembrane Glycoproteins10aMiddle Aged10aPolymorphism, Single Nucleotide10aPregnancy10aReceptors, Interleukin-110aSepsis10aYoung Adult1 aHamann L1 aKumpf O1 aSchuring RP1 aAlpsoy E1 aBedu-Addo G1 aBienzle U1 aOskam L1 aMockenhaupt F1 aSchumann RR00aLow frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy.  a650 v103 a<p><b>BACKGROUND: </b>The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer TIRAP has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.</p><p><b>METHODS: </b>We assessed the TIRAP S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh.</p><p><b>RESULTS: </b>In Ghana, the TIRAP S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous TIRAP 180L tend to increase the risk of sepsis in the German study (P = 0.04).</p><p><b>CONCLUSION: </b>A broad protective effect of TIRAP S180L against infectious diseases per se is not discernible.</p>  a1471-2350