02602nas a2200277   4500000000100000008004100001260001200042653001100054100001800065700001400083700001600097700001500113700002200128700001200150700001400162700001800176700001300194700001600207700001400223245011900237856009900356300001300455490000700468520183500475022001402310       2020                            d  c05/202010aAmazon1 aLeturiondo AL1 aNoronha A1 aMendonça C1 aFerreira C1 aAlvarado-Arnez LE1 aManta F1 aBezerra O1 ade Carvalho E1 aMoraes M1 aRodrigues F1 aTalhari C00aAssociation of NOD2 and IFNG single nucleotide polymorphisms with leprosy in the Amazon ethnic admixed population.  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0008247&type=printable  ae00082470 v143 a<p>Leprosy is a chronic infectious disease, caused by Mycobacterium leprae, which affects skin and peripheral nerves. Polymorphisms in genes associated with autophagy, metabolism, innate and adaptive immunity confer susceptibility to leprosy. However, these associations need to be confirmed through independent replication studies in different ethnicities. The population from Amazon state (northern Brazil) is admixed and it contains the highest proportion of Native American genetic ancestry in Brazil. We conducted a case-control study for leprosy in which we tested fourteen previously associated SNPs in key immune response regulating genes: TLR1 (rs4833095), NOD2 (rs751271, rs8057341), TNF (rs1800629), IL10 (rs1800871), CCDC122/LACC1 (rs4942254), PACRG/PRKN (rs9356058, rs1040079), IFNG (rs2430561), IL6 (rs2069845), LRRK2 (rs7298930, rs3761863), IL23R (rs76418789) and TYK2 (rs55882956). Genotyping was carried out by allelic discrimination in 967 controls and 412 leprosy patients. Association with susceptibility was assessed by logistic regression analyses adjusted for the following covariates: gender, age and ancestry. Genetic ancestry was similar in case and control groups. Statistically significant results were only found for IFNG and NOD2. The rs8057341 polymorphism within NOD2 was identified as significant for the AA genotype (OR = 0.56; 95% CI, 0.37-0.84; P = 0.005) and borderline for the A allele (OR = 0.76; 95% CI, 0.58-1.00; P = 0.053) and carrier (OR = 0.76; 95% CI, 0.58-1.00; P = 0.051). The rs2430561 SNP in IFNG was associated with disease susceptibility for the AT genotype (OR = 1.40; 95% CI, 1.06-1.85; P = 0.018) and carrier (OR = 1.44; 95% CI, 1.10-1.88; P = 0.008). We confirmed that NOD2 and IFNG are major players in immunity against M.leprae in the Amazon ethnic admixed population.</p>  a1935-2735