Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in west Africans.

Meisner, Sarah; Mucklow, Stuart; Warner, G S; Sow, Samba O.; Lienhardt, Christian; Hill, Adrian V. S.

doi:10.4269/ajtmh.2001.65.733

Cited by 69 publications

(57 citation statements)

References 24 publications

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“…[14][15][16][17] Association studies have also demonstrated positive association between this gene and other infectious diseases, for example, leprosy type in the West Africans and human immunodeficiency virus (HIV) infection in Columbians. 18,19 In addition, the SLC11A1 gene also appears associated with autoimmune inflammatory diseases, for example, rheumatoid arthritis (RA) in Canadian Caucasians and Koreans, juvenile rheumatoid arthritis in Latvians, inflammatory bowel disease (IBD) in the Japanese, multiple sclerosis (MS) in South African Caucasians and sarcoidosis in African Americans. [20][21][22][23][24][25] However, some linkage studies failed to demonstrate linkage of the gene to these diseases.…”

Section: Introductionmentioning

confidence: 99%

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

2003

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The SLC11A1 (or NRAMP1) locus on human chromosome 2q35 encodes for the protein solute carrier family 11, member 1. It is expressed in macrophages and involved in the early stages of macrophage priming and activation. Different association studies have shown that the SLC11A1 gene affects susceptibility to infectious diseases and autoimmune inflammatory diseases. Although functional SLC11A1 polymorphisms may account for its role in affecting the susceptibility to these diseases, the positive association can also be because of flanking polymorphisms showing linkage disequilibrium (LD) with this locus. This is the first systematic study to investigate the LD pattern within and around the gene. LD was investigated by genotyping 17 genetic markers in a Chinese population (n ¼ 360). The results indicate that LD is maintained at least 110 kb both upstream and downstream of the locus. The complex LD pattern demands that association studies with SLC11A1 should be carried out with both 5 0 and 3 0 markers. The strong LD between IL8RB and the 5 0 SLC11A1 markers also dictates that IL8RB be tested for association with these diseases. Thus, positive association with SLC11A1 should be interpreted cautiously, and IL8RB should also be considered as a potential candidate susceptibility gene unless proven otherwise.

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Section: Introductionmentioning

confidence: 99%

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

2003

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“…Smaller studies have since found associations between NRAMP1 genotypes and tuberculosis in patients from Japan, Korea and Guinea-Conakry and between NRAMP1 and leprosy type (multibacillary versus paucibacillary) in patients from Mali. [72][73][74][75] It has been found that one of the NRAMP1 polymorphisms, a (GT) n repeat in the 5 0 -untranslated region, influences gene expression, following lipopolysaccharide or IFNg stimulation. 76 Persons who possess the more actively expressed allele have the lowest risk of tuberculosis.…”

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confidence: 99%

Susceptibility to mycobacterial infections: the importance of host genetics

2003

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There is substantial evidence that host genetic factors are important in determining susceptibility to mycobacteria. Several different techniques have been used to identify the genes involved. Studies of an inbred strain of mice with increased susceptibility to mycobacteria, salmonella and leishmania infections led to the identification of the natural resistance-associated macrophage protein gene (Nramp1). Case-control studies have confirmed the importance of the human equivalent of this gene, NRAMP1, and have also suggested that the major histocompatibility complex and vitamin-D receptor genes may be involved in determining human susceptibility to mycobacteria. Studies of individuals with the rare condition of increased susceptibility to disseminated bacille Calmette-Guerin and other atypical mycobacterial infections have identified several abnormalities in the genes encoding the interferon gamma receptor (IFNgR) ligand binding chain, IFNgR signal transduction chain, IFNg signal transduction and activation of transcription-1, interleukin 12 receptor b1 subunit and interleukin 12 p40 subunit. A genome-wide linkage study has been performed to identify genes exerting a major effect on tuberculosis susceptibility in the general population. Linkages were found to markers on chromosomes 15 and X. Studies to identify the genes responsible are in progress.

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“…Estudos para análise da contribuição do fator genético na manutenção da endemia hansênica em algumas áreas do mundo, têm sido desenvolvidos e a utilização de marcadores genéticos moleculares foram empregados até o momento, não só para determinação da influência do componente genético na hanseníase per se, mas também no padrão de resposta imune do hospedeiro à infecção, bem como o complexo mecanismo de efeitos pleitrópicos dos genes candidatos polimórficos, presentes na população de indivíduos infectados e com doença clínica instalada 12,13,14,15 .…”

Section: Introductionunclassified