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Genetic Variants of PTPN2 Gene in Chinese Children with Type 1 Diabetes Mellitus.

ABSTRACT: Several studies have reported the association of PTPN2 gene with type 1 diabetes mellitus (T1DM) in many populations but not in the Chinese Han population. Therefore, the goal of our study was to replicate the reported association between 2 single-nucleotide polymorphisms (SNPs; rs478582 and rs2542151) in the PTPN2 gene and T1DM in Chinese Han children.This case-control study included 141 Chinese Han children with T1DM and 282 healthy controls. Genetic variants of rs478582 and rs2542151 in PTPN2 gene were performed by PCR amplification followed by restriction fragment length polymorphism method.No difference was observed in association of rs478582 in The PTPN2 gene and T1DM. The distribution of allele frequency of rs2542151 differed significantly between T1DM patients and healthy controls (OR, 0.6; 95%CI: 0.44 to 0.95; and P=0.024). Dominant model of rs254215 also was associated with T1DM (OR, 0.6; 95%CI: 0.40 to 0.96; and P=0.032). Younger age at onset in G carriers appeared to increase the risk for T1DM (P=0.030).The findings suggested that rs2542151 SNP in The PTPN2 gene was associated with T1DM in Chinese Han children. Further studies with larger sample sizes involving gene-gene interactions are urgently needed.

SUBMITTER: Peng H

PROVIDER: S-EPMC4566944 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic Variants of PTPN2 Gene in Chinese Children with Type 1 Diabetes Mellitus.

Peng Hui H Li Jiamei J Chen Xiaoyun X Zhou Xiao X Zhu Weiwei W Li Feng F

Medical science monitor : international medical journal of experimental and clinical research 20150907

<h4>Background</h4>Several studies have reported the association of PTPN2 gene with type 1 diabetes mellitus (T1DM) in many populations but not in the Chinese Han population. Therefore, the goal of our study was to replicate the reported association between 2 single-nucleotide polymorphisms (SNPs; rs478582 and rs2542151) in the PTPN2 gene and T1DM in Chinese Han children.<h4>Material and methods</h4>This case-control study included 141 Chinese Han children with T1DM and 282 healthy controls. Gen ...[more]

PMID: 26344020

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Project description:SIRT1 has been demonstrated in nutrient-sensing and insulin-signaling pathways in in vivo and in vitro experiments, but there is minimal information concerning the association between gene polymorphisms of SIRT1 and type 2 diabetes mellitus (T2DM) in a Chinese Han population. Using case-control design, we recruited 310 unrelated T2DM patients from inpatients at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, while 301 healthy controls were volunteers from the community for regular medical checkup. All participants were genotyped within the SIRT1 region. The following five SNPs rs10509291, rs12778366, rs10997870, rs10823112, and rs4746720 cover 100% of common genetic variations (minor allele frequency≥0.05) within the SIRT1 gene (r2≥0.8). The genotypes of SIRT1 gene polymorphisms were analyzed by the Snapshot assay and DNA sequencing. The resulting data show that there was significant genetic differentiation in rs10823112 [p=0.003; OR (95% CI)=1.515 (1.152-1.994) for genotype], rs4746720 [p=0.024; OR (95% CI)=1.37 (1.037-1.674) for genotype], and rs10509291 [p=0.002; OR (95% CI)=1.551 (1.179-2.04) for genotype] between T2DM and control subjects. However, the result of rs4746720 was no longer significant after correction for multiple testing (p after Bonferroni correction=0.12); the results of rs10509291and rs10823112 were still significantly different between the two groups (p after Bonferroni correction=0.01 and 0.015, respectively). Linear regression analyses adjusting for age, gender, and body mass index (BMI) showed that HbA1c and HOMA-IR in subjects with rs10509291 AA genotype were higher than those with TT genotype in T2DM group (p=0.045, p=0.035, respectively). Together, our data show that genetic variation of the SIRT1 gene is related to insulin resistance and increase risk of T2DM in Chinese Han population. The risk allele A at SIRT1 rs10509291 was closely associated with T2DM, and subjects who were homozygous of the A allele were more likely to develop T2DM.

Project description:BackgroundGut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus (T1DM). However, the alterations in the gut microbiota and their correlation with fasting blood glucose (FBG) in Chinese children with T1DM remain unclear.AimTo investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.MethodsSamples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained, to explore the structural and functional alterations in the fecal microbiota. The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument, and the association with FBG were analyzed.ResultsWe found that the bacterial diversity was significantly increased in the T1DM-associated fecal microbiota, and changes in the microbial composition were observed at different taxonomic levels. The T1DM-reduced differential taxa, such as Bacteroides vulgatus ATCC8482, Bacteroides ovatus, Bacteroides xylanisolvens, and Flavonifractor plautii, were negatively correlated with FBG, while the T1DM-enriched taxa, such as Blautia, Eubacterium hallii group, Anaerostipes hadrus, and Dorea longicatena, were positively correlated with FBG. Bacteroides vulgatus ATCC8482, Bacteroides ovatus, the Eubacterium hallii group, and Anaerostipes hadrus, either alone or in combination, could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls. In addition, the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities, such as glycan biosynthesis and metabolism and lipid metabolism, which might play vital roles in the pathogenesis and development of T1DM.ConclusionOur present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.

Project description:ObjectiveInflammation plays a major role in albuminuria in type 2 diabetes mellitus (T2DM). Our previous studies have shown that the expression of vitamin D receptor (VDR) is downregulated in T2DM which is closely associated with the severity of albuminuria. In this study, we investigated the expression of anti-inflammatory cytokine protein tyrosine phosphatase nonreceptor type 2 (PTPN2) in T2DM and explored its relationship to albuminuria and VDR.Methods101 T2DM patients were divided into three groups based on urinary albumin-to-creatinine ratio (uACR): normal albuminuria (uACR < 30 mg/g, n = 29), microalbuminuria (30 mg/g ≤ uACR < 300 mg/g, n = 34), and macroalbuminuria (uACR ≥ 300 mg/g, n = 38). Thirty healthy individuals were included as controls. Serum was analyzed for PTPN2 and IL-6 expression, and peripheral blood mononuclear cells (PBMCs) were analyzed for PTPN2 and VDR expression. THP-1 cells were incubated with high glucose and further treated with or without paricalcitol, a vitamin D analog. The levels of PTPN2, VDR, IL-6, TNFα, and MCP-1 were analyzed. In addition, anti-inflammatory activities of PTPN2 were further explored in THP-1 cells stimulated with high glucose after PTPN2 silencing or overexpression.ResultsPTPN2 expression was downregulated in T2DM with the lowest level observed in macroalbuminuria patients. PTPN2 level positively correlated with VDR but negatively correlated with uACR and IL-6. When stimulated with high glucose, there was an increase in inflammatory factors and a decrease in PTPN2 expression. Treatment with paricalcitol reversed these effects. However, paricalcitol failed to exert anti-inflammatory effects in the setting of PTPN2 knockdown. Thus, low levels of PTPN2 aggravated glucose-stimulated inflammation, while high levels of PTPN2 reduced it.ConclusionPTPN2, an anti-inflammatory factor regulated by VDR, was reduced in T2DM CKD stages 1-2. Taken together, our results suggest that therapeutic strategies that enhance PTPN2 may be beneficial for controlling inflammation in T2DM.

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Genetic Variants of PTPN2 Gene in Chinese Children with Type 1 Diabetes Mellitus.

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Genetic Variants of PTPN2 Gene in Chinese Children with Type 1 Diabetes Mellitus.

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