03109nas a2200565   4500000000100000008004100001260001300042653001500055653001000070653001700080653003700097653002500134653001000159653001800169653004000187653001100227653003200238653001100270653001000281653001200291653001200303653002700315653000900342653001600351653002500367653002600392653003600418653003000454653003000484653001200514653001600526100001200542700001200554700001300566700001200579700001300591700001500604700001300619700001200632700001000644700001100654700001200665700001400677700001300691245013900704300001100843490000800854520166700862022001402529       2013                            d  c2013 Jan10aAdolescent10aAdult10aAge of Onset10aAsian Continental Ancestry Group10aCase-Control Studies10aChild10aEthnic Groups10aEuropean Continental Ancestry Group10aFemale10aGenetic Association Studies10aHumans10aIndia10aIntrons10aleprosy10aLinkage Disequilibrium10aMale10aMiddle Aged10aMolecular Chaperones10aMultivariate Analysis10aPolymorphism, Single Nucleotide10aPromoter Regions, Genetic10aUbiquitin-Protein Ligases10aVietnam10aYoung Adult1 aAlter A1 aFava VM1 aHuong NT1 aSingh M1 aOrlova M1 aVan Thuc N1 aKatoch K1 aThai VH1 aBa NN1 aAbel L1 aMehra N1 aAlcaïs A1 aSchurr E00aLinkage disequilibrium pattern and age-at-diagnosis are critical for replicating genetic associations across ethnic groups in leprosy.  a107-160 v1323 a<p>One of the persistent challenges of genetic association studies is the replication of genetic marker-disease associations across ethnic groups. Here, we conducted high-density association mapping of PARK2/PACRG SNPs with leprosy and identified 69 SNPs significantly associated with leprosy in 198 single-case Vietnamese leprosy families. A total of 56 associated SNPs localized to the overlapping promoter regions of PARK2/PACRG. For this region, multivariate analysis identified four SNPs belonging to two major SNP bins (rs1333955, rs7744433) and two single SNP bins (rs2023004, rs6936895) that capture the combined statistical evidence (P = 1.1 × 10(-5)) for association among Vietnamese patients. Next, we enrolled a case-control sample of 364 leprosy cases and 370 controls from Northern India. We genotyped all subjects for 149 SNPs that capture >80 % of the genetic variation in the Vietnamese sample and found 24 SNPs significantly associated with leprosy. Multivariate analysis identified three SNPs (rs1333955, rs9356058 and rs2023004) that capture the association with leprosy (P < 10(-8)). Hence, two SNPs (rs1333955 and rs2023004) were replicated by multivariate analysis between both ethnic groups. Marked differences in the linkage disequilibrium pattern explained some of the differences in univariate analysis between the two ethnic groups. In addition, the strength of association for two promoter region SNP bins was significantly stronger among young leprosy patients in the Vietnamese sample. The same trend was observed in the Indian sample, but due to the higher age-at-diagnosis of the patients the age effect was less pronounced.</p>  a1432-1203