Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese

Kato, Hitoshi; Nomura, Kyoko; Osabe, Dai; Shinohara, Shuichi; Mizumori, Osamu; Katashima, Rumi; Iwasaki, Shoji; Nishimura, Koichi; Yoshino, Masayasu; Kobori, Masato; Ichiishi, Eiichiro; Nakamura, Naoto; Yoshikawa, Toshikazu; Tanahashi, Takao; Keshavarz, Parvaneh; Kunika, Kiyoshi; Moritani, Maki; Kudo, Eiji; Tsugawa, Kazue; Takata, Yoichiro; Hamada, Daisuke; Yasui, Natsuo; Miyamoto, Tatsuro; Shiota, Hiroshi; Inoue, Hiroshi; Itakura, Mitsuo

doi:10.1016/j.ygeno.2005.11.009

Cited by 35 publications

(28 citation statements)

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“…Finally, there was no significant difference in PRKCH genotype distribution between our controls and a group of Japanese individuals from the same geographic area who had type 2 DM (n ϭ 711), from whom samples were collected for a different genetic association study (ref. 30 and Takata Y: unpublished observations). The mean Ϯ SD age of the type 2 DM group was 62.6 Ϯ 11.4 years, which was not significantly different from that of RA patients in this study.…”

Section: Discussionmentioning

confidence: 75%

“…For this study, we selected gene-based SNPs, also referred to as gene-centric evenly spaced common SNPs (27,30), using the following criteria: suitability for designing high-throughput TaqMan SNP genotyping assays; mapping to the gene-centric region, which we assigned to an interval between 10 kb upstream from the transcription start site and 10 kb downstream from the final exon; an average distance of 10 kb between adjacent SNPs whenever possible; and common SNPs with a minor allele Two-stage association study. For the SNP association study, we applied a 2-stage case-control analysis strategy in 1,900 subjects by randomly assigning them to 2 independent subsets.…”

Section: Methodsmentioning

confidence: 99%

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Genetic association between the PRKCH gene encoding protein kinase Cη isozyme and rheumatoid arthritis in the Japanese population

Takata¹,

Hamada²,

Miyatake³

et al. 2007

Arthritis & Rheumatism

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Objective. Analyses of families with rheumatoid arthritis (RA) have suggested the presence of a putative susceptibility locus on chromosome 14q21-23. This large population-based genetic association study was undertaken to examine this region.Methods. A 2-stage case-control association study of 950 unrelated Japanese patients with RA and 950 healthy controls was performed using >400 genebased common single-nucleotide polymorphisms (SNPs).Results. Multiple SNPs in the PRKCH gene encoding the isozyme of protein kinase C (PKC) showed significant single-locus disease associations, the most significant being SNP c.427؉8134C>T (odds ratio 0.72, 95% confidence interval 0.62-0.83, P ‫؍‬ 5.9 ؋ 10 ؊5 ). Each RA-associated SNP was consistently mapped to 3 distinct regions of strong linkage disequilibrium (i.e., linkage disequilibrium or haplotype blocks) in the PRKCH gene locus, suggesting that multiple causal variants influence disease susceptibility. Significant SNPs included a novel common missense polymorphism of the PRKCH gene, V374I (rs2230500), which lies within the ATP-binding site that is highly conserved among PKC superfamily members. In circulating lymphocytes, PRKCH messenger RNA was expressed at higher levels in resting T cells (CD4؉ or CD8؉) than in B cells (CD19؉) or monocytes (CD14؉) and was significantly down-regulated through immune responses.Conclusion. Our results provide evidence of the involvement of PRKCH as a susceptibility gene for RA in the Japanese population. Dysregulation of PKC signal transduction pathway(s) may confer increased risk of RA through aberrant T cell-mediated autoimmune responses.

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Section: Discussionmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Genetic association between the PRKCH gene encoding protein kinase Cη isozyme and rheumatoid arthritis in the Japanese population

Takata¹,

Hamada²,

Miyatake³

et al. 2007

Arthritis & Rheumatism

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“…Furthermore, SOCS1 or SOCS3 over expression significantly increased plasma insulin levels and perturbed the glucose-lowering effect in insulin tolerance tests. Interestingly, a polymorphism in the non-coding 5' region of the SOCS2 gene is associated with type II diabetes in a Japanese patient population [99]. Whether these effects are related with defects in insulin receptor signaling or insulin secretion remain to be established.…”

Section: Socs Proteins In Rtk Regulated Diseasesmentioning

confidence: 99%

SOCS proteins in regulation of receptor tyrosine kinase signaling

Kazi

Kabir

Flores‐Morales

2014

Cell. Mol. Life Sci.

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SOCS proteins in regulation of receptor tyrosine kinase signaling.Uddin, Kazi; Kabir, Nuzhat N; Flores-Morales, Amilcar; Rönnstrand, Lars Link to publication Citation for published version (APA): Kazi, J. U., Kabir, N. N., Flores-Morales, A., & Rönnstrand, L. (2014). SOCS proteins in regulation of receptor tyrosine kinase signaling. Cellular and Molecular Life Sciences, 71(17), 3297-3310. DOI: 10.1007/s00018-014-1619-y General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. AbstractThe receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many of this family of kinases are overexpressed or mutated in human malignancies and thus became attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressor of cytokine signaling (SOCS) family proteins are well known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7 and CIS. A key feature of this family of proteins is the presence of an SH2 domain and a SOCS box. Recent studies suggest that SOCS proteins also play a role in RTK signaling. Activation of RTK results in transcriptional activation of SOCS encoding genes. These proteins associate with RTKs through their SH2 domains and subsequently recruit the E3 ubiquitin machinery through the SOCS box, and thereby limit receptor stability by inducing ubiquitination. In a similar fashion SOCS proteins negatively regulate mitogenic signaling by RTKs. It is also evident that RTKs sometimes can bypass SOCS regulation and SOCS proteins can even potentiate RTKs-mediated mitogenic signaling. Thus apart from negative regulation of receptor signaling, SOCS proteins may also influence signaling in other ways.

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“…To date, little is known about the impact of SOCS2 on pancreatic physiology. However, it has been recently shown that SOCS2 single nucleotide polymorphisms (SNPs) can be associated with type 2 diabetes [27]. Moreover, the authors found that constitutive production of SOCS2 in MIN6 beta cells reduces glucose-stimulated insulin secretion.…”

Section: Introductionmentioning

confidence: 99%

The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion

et al. 2010

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Aims/hypothesis Suppressor of cytokine signalling (SOCS) proteins are powerful inhibitors of pathways involved in survival and function of pancreatic beta cells. Whereas SOCS1 and SOCS3 have been involved in immune and inflammatory processes, respectively, in beta cells, nothing is known about SOCS2 implication in the pancreas. Methods Transgenic (tg) mice were generated that constitutively produced SOCS2 in beta cells (βSOCS2) to define whether this protein is implicated in beta cell functioning and/or survival.Results Constitutive production of SOCS2 in beta cells leads to hyperglycaemia and glucose intolerance. This phenotype is not a consequence of decreased beta cell mass or inhibition of insulin synthesis. However, insulin secretion to various secretagogues is profoundly altered in intact animals and isolated islets. Interestingly, constitutive SOCS2 production dampens the rise in cytosolic free calcium concentration induced by glucose, while glucose metabolism is unchanged. Moreover, tg islets have a depletion in endoplasmic reticulum Ca 2+ stores, suggesting that SOCS2 interferes with calcium fluxes. Finally, inElectronic supplementary material The online version of this article

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Association of single-nucleotide polymorphisms in the suppressor of cytokine signaling 2 (SOCS2) gene with type 2 diabetes in the Japanese

Cited by 35 publications

References 57 publications

Genetic association between the PRKCH gene encoding protein kinase Cη isozyme and rheumatoid arthritis in the Japanese population

Genetic association between the PRKCH gene encoding protein kinase Cη isozyme and rheumatoid arthritis in the Japanese population

SOCS proteins in regulation of receptor tyrosine kinase signaling

The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion

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