Association of NOD2 and IFNG single nucleotide polymorphisms with leprosy in the Amazon ethnic admixed population

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 ind...

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Published in:	PLoS neglected tropical diseases 2020-05, Vol.14 (5), p.e0008247-e0008247
Main Authors:	Leturiondo, André Luiz, Noronha, Ariani Batista, Mendonça, Carla Yael Ribeiro, Ferreira, Cynthia de Oliveira, Alvarado-Arnez, Lucia Elena, Manta, Fernanda Saloum de Neves, Bezerra, Ohanna Cavalcanti de Lima, Carvalho, Elizeu Fagundes de, Moraes, Milton Ozório, Rodrigues, Fabíola da Costa, Talhari, Carolina
Format:	Article
Language:	eng
Subjects:	Adaptive immunity Adult Age Aged Autophagy Biology and Life Sciences Brazil Case-Control Studies Cell receptors Defence mechanisms Demographic aspects Deoxyribonucleic acid Design Disease resistance DNA Ethnic factors Ethnic groups Female Gender Gene polymorphism Genes Genetic aspects Genetic Predisposition to Disease Genotypes Genotyping Genotyping Techniques Health aspects Humans Immune response Immune system Immunity Infectious diseases Interferon gamma Interferon-gamma - genetics Interleukin 1 Interleukin 10 Interleukin 6 Leprosy Leprosy - genetics LRRK2 protein Male Medicine and Health Sciences Metabolism Middle Aged Minority & ethnic groups Nerves NOD2 protein Nod2 Signaling Adaptor Protein - genetics Nucleotides People and places Peripheral nerves Phagocytosis Physiological aspects Polymorphism Polymorphism, Single Nucleotide Population Regression analysis Single nucleotide polymorphisms Single-nucleotide polymorphism Skin Software Statistical analysis TLR1 protein Toll-like receptors Tumor necrosis factor Tyk2 protein Young Adult
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Summary:	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.
ISSN:	1935-2735 1935-2727 1935-2735