Common Polymorphisms in the NOD2 Gene Region Are Associated with Leprosy and Its Reactive States

• Published in: The Journal of infectious diseases 2010-05, Vol.201 (9), p.1422-1435
• Main Authors: Berrington, William Richard, Macdonald, Murdo, Khadge, Saraswoti, Sapkota, Bishwa Raj, Janer, Marta, Hagge, Deanna Alisa, Kaplan, Gilla, Hawn, Thomas Richard
• Format: Article
• Language: English
• Subjects: Adult; Alleles; BACTERIA; Bacterial diseases; Biological and medical sciences; Case-Control Studies; Erythema Nodosum - genetics; Ethnicity; Female; Fundamental and applied biological sciences. Psychology; Genes; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genotype; Genotypes; Haplotypes - genetics; Human bacterial diseases; Humans; Infections; Infectious diseases; Leprosy; Leprosy - genetics; Leprosy, Lepromatous - genetics; Male; Medical genetics; Medical sciences; Microbiology; Middle Aged; Nepal; Nod2 Signaling Adaptor Protein - genetics; Nod2 Signaling Adaptor Protein - physiology; Polymorphism, Single Nucleotide - genetics; Receptors; Statistical significance; Toll like receptors; Tropical bacterial diseases; Tuberculosis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/651559

Background. Because of its wide spectrum of clinical manifestations and its well-defined immunological complications, leprosy is a useful disease for studying genetic regulation of the host response to infection. We hypothesized that polymorphisms in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene, for a cytosolic receptor known to detect mycobacteria, are associated with susceptibility to leprosy and its clinical outcomes. Methods. We used a case-control study design with 933 patients in Nepal. Our study included 240 patients with type 1 (reversal) reactions and 124 patients with type 2 (erythema nodosum leprosum) reactions.We compared the frequencies of 32 common polymorphisms in the NOD2 gene region between patients with the different clinical types of leprosy as well as between the patients and 101 control participants without leprosy. Results. Four polymorphisms were associated with susceptibility to leprosy when comparing allele frequencies, and 8 were associated when comparing genotype frequencies with a dominant model. Five polymorphisms were associated with protection from reversal reaction in an allelic analysis, and 7 were associated with reversal reaction with a dominant model. Four polymorphisms were associated with increased susceptibility to erythema nodosum leprosum in an allelic analysis, whereas 7 of 32 polymorphisms were associated with a dominant model. Conclusion. These data suggest that NOD2 genetic variants are associated with susceptibility to leprosy and the development of leprosy reactive states.