IL-10 promoter single nucleotide polymorphisms are significantly associated with resistance to leprosy

• Published in: Human genetics 2005-11, Vol.118 (2), p.295-300
• Main Authors: MALHOTRA, Dheeraj, DARVISHI, Katayoon, SOOD, Soni, SHARMA, Swarkar, GROVER, Chander, RELHAN, Vineet, REDDY, B. S. N, BAMEZAI, R. N. K
• Format: Article
• Language: English
• Subjects: Analysis; Bacterial diseases; Biological and medical sciences; Brazil; Case-Control Studies; Chromosomes; Classical genetics, quantitative genetics, hybrids; Disease; DNA Mutational Analysis; Female; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genetic Markers; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes; Human; Human bacterial diseases; Humans; Immunity, Innate - genetics; Immunity, Innate - immunology; Indians, South American; Infections; Infectious diseases; Interleukin-10 - genetics; Leprosy; Leprosy - genetics; Leprosy - immunology; Male; Medical sciences; Molecular and cellular biology; Molecular genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Promoter Regions, Genetic - genetics; Quantitative Trait Loci - genetics; Single nucleotide polymorphisms; Skin; Transcription. Transcription factor. Splicing. Rna processing; Tropical bacterial diseases
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-005-0042-8

The minor haplotype -3575A/-2849G/-2763C in IL-10 promoter has been defined as a marker of disease resistance to leprosy and its severity in Brazilian population. Our investigation of six single-nucleotide polymorphisms (SNPs) in IL-10 promoter in 282 Indian leprosy patients and 266 healthy controls by direct PCR sequencing, however, showed that the extended haplotype: -3575T/-2849G/-2763C/-1082A/-819C/-592C was associated with resistance to leprosy per se and to the development of severe form of leprosy, using either a binomial (controls vs cases, P=0.01, OR=0.58, CI=0.37-0.89) or ordinal (controls vs paucibacillary vs multibacillary, P=0.004) model. Whereas, IL-10 haplotype -3575T/-2849G/-2763C/-1082A/-819T/-592A was associated with the risk of development of severe form of leprosy (P=0.0002) in contrast to the minor risk haplotype -3575T/-2849A/-2763C in the Brazilian population. The role of IL-10 promoter SNPs in Brazilian and Indian population strongly suggests the involvement of IL-10 locus in the outcome of leprosy.