Genetic variants in mannose receptor gene (MRC1) confer susceptibility to increased risk of sarcoidosis

Hattori, Takeshi; Konno, Satoshi; Takahashi, A; Isada, Akira; Shimizu, Kaoruko; Shimizu, Kenichi; Taniguchi, Natsuko; Gao, Peisong; Yamaguchi, Etsuro; Hizawa, Nobuyuki; Huang, Shau Ku; Nishimura, Masaharu

doi:10.1186/1471-2350-11-151

Cited by 25 publications

(18 citation statements)

References 27 publications

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“…The MRC1 gene is found on chromosome 10p12 in the vicinity of other genes associated with sarcoidosis and Crohn's disease [66]. A polymorphism of MRC1 with a remarkable odds ratio of 2.53 for sarcoidosis has been identified in a Japanese study, which is, however, also involved in other inflammatory disorders [113]. The extent of serum angiotensin converting enzyme (sACE) increase appears to reflect the total body granuloma load [114].…”

Section: Geneticsmentioning

confidence: 98%

Pathogenesis of sarcoidosis

Müller–Quernheim¹,

Prasse²,

Zissel³

2012

La Presse Médicale

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Section: Geneticsmentioning

confidence: 98%

Pathogenesis of sarcoidosis

Müller–Quernheim¹,

Prasse²,

Zissel³

2012

La Presse Médicale

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“…mannose, fucose and N-acetyl-glucosamine (Shepherd et al, 1982). The MR is currently recognized as a prototypic PRR expressed on macrophages, some dendritic cells (Sallusto et al, 1995) and other cell types (Stahl and Ezekowitz, 1998), orchestrating innate and adaptive immune communication (He et al, 2007), and is emerging as a critical regulator of health and disease (Lee et al, 2002; Zhang et al, 2012; Hattori et al, 2010; Hattori et al, 2009). Despite its well-known central role in host recognition of a variety of microbes and ability to modulate inflammatory responses, its receptor-specific role in transducing signals to regulate phagocytosis and inflammatory pathways remains in question (Le Cabec et al, 2005; Gazi and Martinez-Pomares, 2009; Goyal et al, 2016; Hoving et al, 2014; Martinez-Pomares, 2012; Sancho and Reis E Sousa, 2012, Taylor et al, 2005; Gordon, 2016).…”

Section: Introductionmentioning

confidence: 99%

M. tuberculosis -Initiated Human Mannose Receptor Signaling Regulates Macrophage Recognition and Vesicle Trafficking by FcRγ-Chain, Grb2, and SHP-1

et al. 2017

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Summary Despite its prominent role as C-type lectin (CTL) pattern recognition receptor, mannose receptor (MR, CD206)-specific signaling molecules and pathways are unknown. The MR is highly expressed on human macrophages, regulating endocytosis, phagocytosis and immune responses, and mediating Mycobacterium tuberculosis (M.tb) phagocytosis by human macrophages thereby limiting phagosome-lysosome (P-L) fusion. We identified human MR-associated proteins using phosphorylated and non-phosphorylated MR cytoplasmic tail peptides. We found that MR binds FcRγ-chain, which is required for MR plasma membrane localization and M.tb cell association. Additionally, we discovered that MR-mediated M.tb association triggers immediate MR tyrosine residue phosphorylation and Grb2 recruitment, activating the Rac/Pak/Cdc-42 signaling cascade important for M.tb uptake. MR activation subsequently recruits SHP-1 to the M.tb-containing phagosome, where its activity limits PI(3)P generation at the phagosome and M.tb P-L fusion, and promotes M.tb growth. In sum, we identify human MR signaling pathways that temporally regulate phagocytosis and P-L fusion during M.tb infection.

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“…The MRC1 gene played an active role in innate and adaptive immunity and was naturally proposed to be a candidate gene at the chromosomal region 10p13 that was associated with leprosy (Mira et al 2003;Siddiqui et al 2001). Genetic variants of the MRC1 gene have also been reported to confer susceptibility to increased risk of sarcoidosis (Hattori et al 2010). Despite that we failed to validate the reported association of rs1926736 (p.G396S) of the MRC1 gene with leprosy (Alter et al 2010), we identified two other SNPs in the intron region of this gene that confer a susceptibility to leprosy.…”

Section: Discussionmentioning

confidence: 98%

Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy in Han Chinese from Southwest China

Wang

Feng

et al. 2012

Hum Genet

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Leprosy is an ancient infectious disease, with over 200,000 affected people (mainly in Asia and Africa) being registered annually. Genetic factors may confer susceptibility to this disease. In the present study, we genotyped 12 genetic variants of the MRC1 gene and the IFNG gene in 527 Han Chinese with leprosy and 583 healthy individuals from Yunnan, China, to discern potential association of these two genes with leprosy. In particular, we aimed to validate the recently reported association of MRC1 variant rs1926736 (p.G396S) and IFNG variant rs2430561 (+874 T>A) with leprosy, which were initially observed in Vietnamese and Brazilian populations, respectively. Our results failed to confirm the reported association between variants rs1926736 and rs2430561 and leprosy in Han Chinese. However, we found that variants rs692527 (P = 0.022) and rs34856358 (P = 0.022) of the MRC1 gene were associated with paucibacillary leprosy, and rs3138557 of the IFNG gene was significantly associated with multibacillary leprosy. The exact role of the MRC1 gene and the IFNG gene in leprosy awaits future study.

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Genetic variants in mannose receptor gene (MRC1) confer susceptibility to increased risk of sarcoidosis

Cited by 25 publications

References 27 publications

Pathogenesis of sarcoidosis

Pathogenesis of sarcoidosis

M. tuberculosis -Initiated Human Mannose Receptor Signaling Regulates Macrophage Recognition and Vesicle Trafficking by FcRγ-Chain, Grb2, and SHP-1

Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy in Han Chinese from Southwest China

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