03449nas a2200709   4500000000100000008004100001260001600042653002200058653004100080653000900121653003700130653003500167653003600202653002500238653003100263653001100294653003200305653001700337653003800354653003400392653001100426653002100437653001200458653000900470653001600479653003600495653002400531100001000555700001000565700001400575700000900589700000900598700000900607700000900616700001000625700001000635700000900645700001200654700001100666700000900677700001000686700001100696700001000707700001100717700001000728700000900738700001000747700001100757700001000768700001100778700001100789700001200800700001000812700001200822245009300834856007900927300001101006490000701017050001301024520168801037022001402725       2013                            d  c2013 Nov 0110aAdaptive Immunity10aAdaptor Proteins, Signal Transducing10aAged10aAsian Continental Ancestry Group10aB-Cell CLL-Lymphoma 10 Protein10aCARD Signaling Adaptor Proteins10aCase-Control Studies10aChromosomes, Human, Pair 110aFemale10aGenetic Association Studies10aGenetic Loci10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aImmunity, Innate10aleprosy10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aToll-Like Receptors1 aLiu H1 aBao F1 aIrwanto A1 aFu X1 aLu N1 aYu G1 aYu Y1 aSun Y1 aLow H1 aLi Y1 aLiany H1 aYuan C1 aLi J1 aLiu J1 aChen M1 aLiu H1 aWang N1 aYou J1 aMa S1 aNiu G1 aZhou Y1 aChu T1 aTian H1 aChen S1 aZhang X1 aLiu J1 aZhang F00aAn association study of TOLL and CARD with leprosy susceptibility in Chinese population.  uhttp://hmg.oxfordjournals.org/content/early/2013/06/19/hmg.ddt286.full.pdf  a4430-70 v22  aLIU 20133 a<p>Previous genome-wide association studies (GWASs) identified multiple susceptibility loci that have highlighted the important role of TLR (Toll-like receptor) and CARD (caspase recruitment domain) genes in leprosy. A large three-stage candidate gene-based association study of 30 TLR and 47 CARD genes was performed in the leprosy samples of Chinese Han. Of 4363 SNPs investigated, eight SNPs showed suggestive association (P < 0.01) in our previously published GWAS datasets (Stage 1). Of the eight SNPs, rs2735591 and rs4889841 showed significant association (P < 0.001) in an independent series of 1504 cases and 1502 controls (Stage 2), but only rs2735591 (next to BCL10) showed significant association in the second independent series of 938 cases and 5827 controls (Stage 3). Rs2735591 showed consistent association across the three stages (P > 0.05 for heterogeneity test), significant association in the combined validation samples (Pcorrected = 5.54 × 10(-4) after correction for 4363 SNPs tested) and genome-wide significance in the whole GWAS and validation samples (P = 1.03 × 10(-9), OR = 1.24). In addition, we demonstrated the lower expression of BCL10 in leprosy lesions than normal skins and a significant gene connection between BCL10 and the eight previously identified leprosy loci that are associated with NFκB, a major regulator of downstream inflammatory responses, which provides further biological evidence for the association. We have discovered a novel susceptibility locus on 1p22, which implicates BCL10 as a new susceptibility gene for leprosy. Our finding highlights the important role of both innate and adaptive immune responses in leprosy. </p>  a1460-2083