Association of Common Genetic Variants in Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 with Type 2 Diabetes Mellitus in a Chinese Han Population

Li, Tingting; Qiao, Hong; Tong, Huixin; Zhuang, Tianwei; Wang, Tongtong

doi:10.4103/0366-6999.181969

Cited by 5 publications

(5 citation statements)

References 16 publications

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“…Moreover, the MAP4K4 SNPs (rs2236936 and rs2236935) are associated with reduced insulin release only in lean subjects (BMI < 25). Consistently, the association of MAP4K4 genetic variants with T2D using 1,972 samples from Chinese Han population was also reported; this population is mainly non-obese individuals (average BMI < 27.5 in both the T2D subgroup and control subgroup) [32]. The MAP4K4 SNP rs2236935 in the MAP4K4 gene is associated with T2D.…”

Section: Main Textmentioning

confidence: 56%

“…The MAP4K4 SNP rs2236935 in the MAP4K4 gene is associated with T2D. In contrast, the MAP4K4 SNP rs11674694 that associates with insulin resistance and T2D in European population is not associated with T2D in Chinese population [32]. These two results [31, 32] reflect that distinct MAP4K4 SNPs are associated with T2D in different ethnic groups.…”

Section: Main Textmentioning

confidence: 99%

“…In contrast, the MAP4K4 SNP rs11674694 that associates with insulin resistance and T2D in European population is not associated with T2D in Chinese population [32]. These two results [31, 32] reflect that distinct MAP4K4 SNPs are associated with T2D in different ethnic groups. In addition, using genome-wide analysis of DNA methylation, Yamada et al reported that the MAP4K4 promoter is hypermethylated in Japanese patients with atherosclerosis, which is one of the fatal complications associated with T2D [33].…”

Section: Main Textmentioning

confidence: 99%

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MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes

Chuang

Tan

2017

J Biomed Sci

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Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6+ Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.

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Section: Main Textmentioning

confidence: 56%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

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MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes

Chuang

Tan

2017

J Biomed Sci

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“…Significantly, nine genes (C1orf141, CALU, CCDC136, FGF2, LOC101927051, MAP4K4, MPZL3, PAPOLG, and SH3BP1) were found to be associated with more than one disease in the VEGAS2 analysis, although these genes had never been reported to be associated with any autoimmune/autoinflammatory disease in previous GWAS. MAP4K4 has been enriched in several GO terms including MAP kinase c kinase activity (GO:0008349), which is an important contributor to the risk of developing type 2 diabetes mellitus in a Chinese Han population (51). In addition, Aouadi et al (52) demonstrated that orally delivered small interfering RNA targeting macrophage MAP4K4 suppresses systemic inflammation, thus implicating this technology as a new strategy to attenuate inflammatory responses in human disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of 67 Pleiotropic Genes Associated With Seven Autoimmune/Autoinflammatory Diseases Using Multivariate Statistical Analysis

et al. 2020

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Although genome-wide association studies (GWAS) have a dramatic impact on susceptibility locus discovery, this univariate approach has limitations in detecting complex genotype-phenotype correlations. Multivariate analysis is essential to identify shared genetic risk factors acting through common biological mechanisms of autoimmune/autoinflammatory diseases. In this study, GWAS summary statistics, including 41,274 single nucleotide polymorphisms (SNPs) located in 11,516 gene regions, were analyzed to identify shared variants of seven autoimmune/autoinflammatory diseases using the metaCCA method. Gene-based association analysis was used to refine the pleiotropic genes. In addition, GO term enrichment analysis and protein-protein interaction network analysis were applied to explore the potential biological functions of the identified genes. A total of 4,962 SNPs (P < 1.21 × 10 −6) and 1,044 pleotropic genes (P < 4.34 × 10 −6) were identified by metaCCA analysis. By screening the results of gene-based P-values, we identified the existence of 27 confirmed pleiotropic genes and highlighted 40 novel pleiotropic genes that achieved statistical significance in the metaCCA analysis and were also associated with at least one autoimmune/autoinflammatory in the VEGAS2 analysis. Using the metaCCA method, we identified novel variants associated with complex diseases incorporating different GWAS datasets. Our analysis may provide insights for the development of common therapeutic approaches for autoimmune/autoinflammatory diseases based on the pleiotropic genes and common mechanisms identified.

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“…Specifically, 100 pairs of blind duplicates were performed with a concordance rate >98%. [ 16 ] Moreover, these variants exhibited allelic frequencies >15% in Han Chinese (National Center for Biotechnology Information dbSNP database: https://www.ncbi.nlm.nih.gov/snp/ ).…”

Section: Ethodsmentioning

confidence: 99%

Relationship between Modulator Recognition Factor 2/AT-rich Interaction Domain 5B Gene Variations and Type 2 Diabetes Mellitus or Lipid Metabolism in a Northern Chinese Population

Sun

Zhang

Chen

et al. 2017

Chinese Medical Journal

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Background:Four single nucleotide polymorphisms (SNPs) in the modulator recognition factor 2/AT-rich interaction domain 5B (MRF2/ARID5B) gene located at chromosome 10q21.2 have been shown to be associated with both type 2 diabetes mellitus (T2DM) and coronary artery disease in a Japanese cohort. This study aimed to investigate the relationship between these SNPs (rs2893880, rs10740055, rs7087507, rs10761600) and new-onset T2DM and lipid metabolism in a Northern Chinese population.Methods:This was a case-control study. The rs2893880, rs10740055, rs7087507, and rs10761600 genetic variants were genotyped by SNPscan and analyzed in relation to T2DM susceptibility in 2000 individuals (999 with newly diagnosed T2DM and 1001 controls without diabetes mellitus). Associations between the MRF2/ARID5B genetic models and T2DM were determined by multivariate logistic regression.Results:Regarding the rs10740055 SNP, AA was associated with a higher risk of T2DM compared with codominant-type CC (adjusted by sex, age, and body mass index [BMI], P = 0.041, odds ratio [OR] = 1.421, 95% confidence interval [CI] 1.014–1.991). Meanwhile, AA individuals were at increased risk of presenting with T2DM compared with individuals with CC or a single C (adjusted by sex, age, and BMI, P = 0.034, OR = 1.366, 95% CI 1.023–1.824). With respect to rs10761600, AT contributed to a higher risk of T2DM compared with AA (adjusted by sex, age, and BMI, P = 0.013, OR = 1.585, 95% CI 1.101–2.282), while TT also increased the risk of presenting with T2DM compared with AA or A (adjusted by sex, age, and BMI, P = 0.004, OR = 1.632, 95% CI 1.166–2.284). High-density lipoprotein cholesterol (HDL-C) levels were significantly different among the three genotypes of rs7087507 in the controls (P = 0.048) (GG>GA).Conclusions:The present results identified MRF2/ARID5B as a potential susceptibility gene for new-onset T2DM in a Northern Chinese population, while the rs7087507 SNP was associated with HDL-C levels. Further larger studies are required to validate these findings.

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Association of Common Genetic Variants in Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 with Type 2 Diabetes Mellitus in a Chinese Han Population

Cited by 5 publications

References 16 publications

MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes

MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes

Identification of 67 Pleiotropic Genes Associated With Seven Autoimmune/Autoinflammatory Diseases Using Multivariate Statistical Analysis

Relationship between Modulator Recognition Factor 2/AT-rich Interaction Domain 5B Gene Variations and Type 2 Diabetes Mellitus or Lipid Metabolism in a Northern Chinese Population

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