Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471

Alm, Johan; Sanjeevi, Carani B.; Miller, E.N.; Dabadghao, P.; Lilja, G.; Pershagen, Göran; Blackwell, Jenefer M.; Scheynius, Annika

doi:10.1038/sj.gene.6363834

Cited by 30 publications

(26 citation statements)

References 45 publications

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“…On a global scale, the (GT) 9 allele has a frequency range of 0.65-0.75 in Afrikaners, 24 African Americans 25 and Caucasians (including the Swedish, 45 Latvians 22 and Columbians 19 ), and of 0.80-0.90 in Africans and Asians (including Chinese, Koreans, 21 Vietnamese, 46 Indians 47 and the Japanese 17,23 ). The (GT) 10 allele (or allele 2) ranks second in frequency (0.10-0.35), while the classical (GT) 11 allele (or allele 1) is usually the least frequent (o0.05).…”

Section: Resultsmentioning

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: Resultsmentioning

confidence: 99%

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

2003

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“…Perhaps polymorphisms in the human NRAMP1 gene, and other infection-related genes, could contribute to the inverse correlation between bacterial infection and allergic diseases. Polymorphisms in the genomic region of human NRAMP1 are associated with the risk of atopy in BCG-vaccinated children [23]. Moreover, the Nramp1 gene is involved in several other diseases of deregulated immunity: a polymorphism in the promoter region of NRAMP1 has been associated with inflammatory bowel disease [24], rheumatoid arthritis [25], multiple sclerosis [26] and type 1 diabetes mellitus [27].…”

Section: Infectious Agents and The Hygiene Hypothesismentioning

confidence: 99%

Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis

Smit¹,

Folkerts

Nijkamp

2004

Trends in Immunology

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“…Other investigators already suggested that polymorphisms in the genomic region of NRAMP1 are associated with risk of atopy in BCG-vaccinated children (20). The current controversy about the efficacy of mycobacteria and their components in the treatment of allergic asthma in humans (46,47) can be explained by the strong influence of genetic factors, such as the NRAMP1 gene, on the inverse relationship between infection and the development of allergic disease.…”

Section: Cd25mentioning

confidence: 99%

“…In humans, association or linkage of NRAMP1 with susceptibility to infectious diseases, but also atopy and autoimmune disease, has been demonstrated (20,21). The murine polymorphism of Nramp1 is apparent as either low (Nramp1 s ) or high (Nramp1 r ) resistance of macrophages to the growth of intracellular organisms.…”

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confidence: 99%

The Slc11a1 (Nramp1) Gene Controls Efficacy of Mycobacterial Treatment of Allergic Asthma

Smit

Loveren

Hoekstra

et al. 2003

The Journal of Immunology

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Genes controlling antibacterial resistance may be important in the hygiene hypothesis, which states that lack of bacterial infections during childhood would favor development of allergic disease. We, therefore, studied whether Nramp1 (Slc11a1) alleles, which determine susceptibility (Nramp1s) or resistance (Nramp1r) to intracellular bacteria, affect the efficacy of heat-killed Mycobacterium vaccae in the treatment of allergic asthma in a mouse model. Treatment of OVA-sensitized Nramp1s mice with M. vaccae suppressed airway hyperresponsiveness, airway eosinophilia, Ag-specific IgE, and IL-4 and IL-5 production after OVA aerosol challenge. In contrast, M. vaccae hardly affected these parameters in Nramp1r mice. In addition, The Nramp1 gene affected both T cell-mediated responses to M. vaccae in vivo and the level of macrophage activation after stimulation with M. vaccae in vitro. In conclusion, the efficacy of M. vaccae in preventing allergic and asthmatic manifestations in a mouse model is strongly affected by Nramp1 alleles. These findings could have important implications for the future use of mycobacteria and their components in the prevention or treatment of allergic asthma. A new link is described between genes, the environment, and the development of allergy, in which the Nramp1 gene fine tunes the hygiene hypothesis.

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Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471

Abstract: The influence of the SLC11A1 (formerly NRAMP1) gene on the association between BCG vaccination and atopy in children was studied in 179 children, BCG vaccinated in infancy, and 307 children without BCG vaccination, all

Cited by 30 publications

References 45 publications

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis

The Slc11a1 (Nramp1) Gene Controls Efficacy of Mycobacterial Treatment of Allergic Asthma

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