03090nas a2200781   4500000000100000008004100001653002700042653005900069653002900128653003300157653003600190653003500226653001600261653000900277653002700286653001200313653001100325653001500336653003400351653003800385653001100423653002300434653003200457653002500489653000900514100001200523700001000535700001100545700001000556700001000566700001000576700001000586700000900596700000900605700000900614700000900623700001000632700001100642700001000653700000900663700000900672700000900681700001000690700001100700700001000711700001000721700001200731700001000743700001100753700001100764700001100775700001100786700001200797700001100809700001000820700001000830700001200840700001200852700001500864700001100879700001000890700001200900245009600912300001201008490000701020520126701027022001402294       2011                            d10aReceptors, Interleukin10aReceptor-Interacting Protein Serine-Threonine Kinase 210arab GTP-Binding Proteins10aPrincipal Component Analysis10aPolymorphism, Single Nucleotide10aNod2 Signaling Adaptor Protein10aMiddle Aged10aMale10aLinkage Disequilibrium10aleprosy10aHumans10aHaplotypes10aGenome-Wide Association Study10aGenetic Predisposition to Disease10aFemale10aEpistasis, Genetic10aChromosomes, Human, Pair 1110aCase-Control Studies10aAged1 aZhang F1 aLiu H1 aChen S1 aLow H1 aSun L1 aCui Y1 aChu T1 aLi Y1 aFu X1 aYu Y1 aYu G1 aShi B1 aTian H1 aLiu D1 aYu X1 aLi J1 aLu N1 aBao F1 aYuan C1 aLiu J1 aLiu H1 aZhang L1 aSun Y1 aChen M1 aYang Q1 aYang H1 aYang R1 aZhang L1 aWang Q1 aLiu H1 aZuo F1 aZhang H1 aKhor CC1 aHibberd ML1 aYang S1 aLiu J1 aZhang X00aIdentification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy.  a1247-510 v433 a<p>We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10(-14), OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10(-11), OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-κB pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.</p>
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