JAZF1, a relevant metabolic regulator in type 2 diabetes

Liao, Zhe-Zhen; Wang, Yadi; Qi, Xiaoyan; Xiao, Xinhua

doi:10.1002/dmrr.3148

Cited by 32 publications

(32 citation statements)

References 43 publications

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“…The other five susceptibility genes that contributed to EOD, CDKAL1 , CDKN2BAS , CDC123/CAMK1D , HHEX , and KCNQ1 are essential in β‐cell function . Among genes that contributed to LOD, JAZF1 functions in inflammation, gluconeogenesis, insulin sensitivity, lipid metabolism, and β‐cell apoptosis; TCF7L2 affects β‐cell function and survival, and CENTD2 is associated with decreased glucose‐stimulated insulin release …”

Section: Discussionmentioning

confidence: 99%

Early‐onset type 2 diabetes is associated with genetic variants of β‐cell function in the Chinese Han population

Kong

Zhang

Hong

et al. 2019

Diabetes Metabolism Res

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Aims:To investigate the genetic factors contributing to early-onset type 2 diabetes (EOD) in the Chinese Hans populations. Materials and methods:For 2734 newly diagnosed type 2 diabetes patients and 4041 normal glycemic controls, 25 single nucleotide polymorphisms from 24 genomic loci linked to diabetes were successfully genotyped. Three genetic risk scores (GRSs) were constructed, including the weighted type 2 diabetes-related GRS (wT-GRS), the weighted β-cell function-related GRS (wB-GRS), and the weighted GRS constructed by risk alleles not related to β-cell function (wNB-GRS).For patients with diabetes, EOD, middle-age-onset type 2 diabetes (MOD), and late-onset type 2 diabetes (LOD) were defined by onset ages ≤40, 40 to 60, and ≥60 years, respectively.Results: From single marker analysis, different gene profiles were identified between EOD and LOD patients. EOD patients had greater wT-GRS and wB-GRS values than LOD patients. After adjustment for sex, elevated wT-GRS and wB-GRS values were significantly associated with an increased risk for EOD by 1.11-and 1.21-fold per allele (P = 1.69 × 10 −7 ; 6.07 × 10 −8 ). The wT-GRS and wNB-GRS were nominally related to an increased risk of LOD by 1.03-fold per allele (P = 1.03 × 10 −2 , 1.78 × 10 −2 ). In patients with diabetes, higher wT-GRS and wB-GRS were associated with younger onset age [wT-GRS: β (SE) = -0.0033(0.0016), P = 3.74 × 10 −2 ; wB-GRS: −0.0076(0.0028), 7.45 × 10 −3 ] and decreased insulinogenic index [wT-GRS: -0.0384(0.0098), 9.39 × 10 −5 ; wB-GRS: −0.0722(0.0176), 4.21 × 10 −5 ]. Conclusion:Our findings indicate a strong genetic predisposition for EOD, which can be mainly attributed to genetic variants linked to β-cell function, suggesting the β-cell dysfunction plays a key role in the pathogenesis of EOD in Chinese Han individuals.

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Section: Discussionmentioning

confidence: 99%

Early‐onset type 2 diabetes is associated with genetic variants of β‐cell function in the Chinese Han population

Kong

Zhang

Hong

et al. 2019

Diabetes Metabolism Res

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“…International Publisher 2 mRNA-binding protein 2 (IGF2BP2), which are expressed in insulin-resistant tissue, are involved in lipid metabolism and are associated with insulin resistance [7,8,[13][14][15][16][17][18]. In adipocytes, JAZF1 inhibits the accumulation of fatty acids and triglycerides [15].…”

Section: Ivyspringmentioning

confidence: 99%

“…In addition to the indirect role of JAZF1, IGF1, and IGF2BP2 in insulin resistance involving lipid metabolism, the three proteins can also have direct effects on glucose metabolism [5,16,19]. The genes encoding these proteins, as well as their SNPs, have been associated with T2DM and metabolic traits [6,11,[20][21][22][23][24][25][26].…”

Section: Ivyspringmentioning

confidence: 99%

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Evidence of association between single-nucleotide polymorphisms in lipid metabolism-related genes and type 2 diabetes mellitus in a Chinese population

et al. 2021

Int. J. Med. Sci.

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Background: Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder triggered by insulin resistance in peripheral tissues. Evidence has shown that lipid metabolism and related genetic factors lead to insulin resistance. Hence, it is meaningful to investigate the association between single-nucleotide polymorphisms (SNPs) in lipid metabolism-related genes and T2DM. Methods: A total of 1,194 subjects with T2DM and 1,274 Non-diabetic subjects (NDM) were enrolled. Five SNPs in three genes (rs864745 in JAZF1 , rs35767 in IGF1 , and rs4376068, rs4402960, and rs6769511 in IGF2BP2 ) that contribute to insulin resistance involving lipid metabolism were genotyped using the MassArray method in a Chinese population. Results: The allele and genotypes of rs6769511 in IGF2BP2 were associated with T2DM (P=0.009 and P=0.002, respectively). In inheritance model analysis, compared with the T/T-C/T genotype, the C/C genotype of rs6769511 in IGF2BP2 was a risk factor for the development of T2DM (P<0.001, odds ratio [OR] =1.76; 95% confidence interval [CI]: 1.29-2.42). Haplotype analysis revealed associations of the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 with the development of T2DM (P=0.015). Additionally, rs4376068C-rs4402960T-rs6769511C was a risk haplotype for T2DM (OR=1.179; 95% CI: 1.033-1.346). Conclusion: The rs6769511 in IGF2BP2 was associated with T2DM susceptibility, and the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 was associated with the development of T2DM in a Chinese population.

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“…Similarly, several other cytokine-related genes have been associated with diabetes or other clinical metabolic traits in several GWAS: MAPK8IP1 , implicated in interleukin (IL)-1 induced apoptosis beta cells [ 45 ] and IFNGR1 (CD119), encoding the gamma interferon cytokine receptor [ 44 ]. GWAS also revealed genes involved in inflammatory signalling pathways, inside pancreatic endocrine islets, adipocytes or more systemically in the pathophysiology of metabolic syndrome leading to T2D: ST6GAL1 , involved in cell-surface antigens production [ 46 ], JAZF1 , a regulator of inflammation in adipose tissue [ 47 ], two inflammatory genes MAP3K1 in JNK pathway [ 48 ] or MACROD1 as a NF-κB regulator [ 48 ], NFE2L3 , implicated in cellular stress responses [ 50 ] and TLR4 , from the toll-like receptor family, activating the intra-cellular NF-κB pathways [ 44 ] ( Table 1 ). Continuing to increase the number of included individuals, and the coverage of the genome, a more recent study, including nearly one million Europeans, doubled the number of T2D-associated signals, up to 403, from common alleles through rare variants, including 19 protein-coding variants corresponding to 18 distinct genes ( PATJ , GCKR , SCD5 , ANKH , PAM , MRPS30 , POC5 , RREB1 , SLC30A8 , NEUROG3 , QSER1 , CDKN1B , WSCD2 , HNF1A , IRS2 , ZNF771 , APOE and HNF4A ) [ 49 ].…”

Section: Inflammation In Diabetes: Genetic Evidencementioning

confidence: 99%

Regulation of inflammation in diabetes: From genetics to epigenomics evidence

Diedisheim

Carcarino

Vandiedonck

et al. 2020

Molecular Metabolism

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Background Diabetes is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of preventive and therapeutic approaches. Genetic and environmental factors are the culprits involved in diabetes risk. Evidence from the last decade has highlighted that deregulation in the immune and inflammatory responses increase susceptibility to type 1 and type 2 diabetes. Spatiotemporal patterns of gene expression involved in immune cell polarisation depend on genomic enhancer elements in response to inflammatory and metabolic cues. Several studies have reported that most regulatory genetic variants are located in the non-protein coding regions of the genome and particularly in enhancer regions. The progress of high-throughput technologies has permitted the characterisation of enhancer chromatin properties. These advances support the concept that genetic alteration of enhancers may influence the immune and inflammatory responses in relation to diabetes. Scope of review Results from genome-wide association studies (GWAS) combined with functional and integrative analyses have elucidated the impacts of some diabetes risk-associated variants that are involved in the regulation of the immune system. Additionally, genetic variant mapping to enhancer regions may alter enhancer status, which in turn leads to aberrant expression of inflammatory genes associated with diabetes susceptibility. The focus of this review was to provide an overview of the current indications that inflammatory processes are regulated at the genetic and epigenomic levels in diabetes, along with perspectives on future research avenues that may improve understanding of the disease. Major conclusions In this review, we provide genetic evidence in support of a deregulated immune response as a risk factor in diabetes. We also argue about the importance of enhancer regions in the regulation of immune cell polarisation and how the recent advances using genome-wide methods for enhancer identification have enabled the determination of the impact of enhancer genetic variation on diabetes onset and phenotype. This could eventually lead to better management plans and improved treatment responses in human diabetes.

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JAZF1, a relevant metabolic regulator in type 2 diabetes

Cited by 32 publications

References 43 publications

Early‐onset type 2 diabetes is associated with genetic variants of β‐cell function in the Chinese Han population

Early‐onset type 2 diabetes is associated with genetic variants of β‐cell function in the Chinese Han population

Evidence of association between single-nucleotide polymorphisms in lipid metabolism-related genes and type 2 diabetes mellitus in a Chinese population

Regulation of inflammation in diabetes: From genetics to epigenomics evidence

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