02835nas a2200325   4500000000100000008004100001260001200042653001800054653001700072653002500089653001200114653002700126653001900153100001400172700001300186700001500199700001400214700001200228700001500240700001300255700001500268700002200283700001400305700001600319700001100335700002000346245009300366520203600459022001402495       2020                            d  c11/202010aHLA-B alleles10aMICA alleles10agenetic polymorphism10aleprosy10alinkage disequilibrium10aImmunogenetics1 aJarduli L1 aAlves HV1 ade Souza V1 aSartori P1 aFava VM1 ade Souza F1 aMarcos E1 aPereira AC1 aDias-Baptista IMF1 aVirmond M1 ade Moraes M1 aMira M1 aVisentainer JEL00aAssociation of MICA and HLA-B alleles with leprosy in two endemic populations in Brazil.3 a<p>Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case-control and a family-based study in two endemic populations in Brazil. MICA and HLA-B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR-SSOP-Luminex-based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3'/5'untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi-square or Fisher's exact test together with a multivariate analysis. Family-based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002-HLA-B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA-A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA-B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA-B markers rs2596498 and rs2507992, and high LD (R  = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA-B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele.</p>  a1744-313X