Obesity-related loci in TMEM18, CDKAL1 and FAIM2 are associated with obesity and type 2 diabetes in Chinese Han patients

Kang, Jian; Guan, Renchu; Zhao, Ying; Chen, Yan

doi:10.1186/s12881-020-00999-y

Cited by 16 publications

(12 citation statements)

References 38 publications

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“…GALNT7 is involved in several transcriptional networks, including the one involving the competing endogenous RNA TP73-AS1 —which sequesters miR-103a, and RP11-798M19.6 . There is evidence that FAIM2 expression may increase susceptibility to type 2 diabetes associated with obesity [ 52 ] and to obstructive sleep apnea-related cardiac injury [ 53 ], thus, the FAIM2 downregulation (found in TRA subjects) appears to bear favorable effects.…”

Section: Resultsmentioning

confidence: 99%

Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

Sanctis

Filardo

Abruzzo

et al. 2021

IJMS

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In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared—the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.

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Section: Resultsmentioning

confidence: 99%

Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

Sanctis

Filardo

Abruzzo

et al. 2021

IJMS

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“…CDKAL1 is associated with proinsulin conversion and insulin response upon glucose stimulation 34 and is necessary for normal mitochondrial morphology and adipose tissue function 33 . In recent studies, the CDKAL1 rs7754840 variant was shown to be associated with increased waist circumference and waist-to-hip ratio in Chinese Han patients 35 , and the CDKAL1 rs2206734 polymorphism was shown to be an independent predictor of the MUHNW phenotype in Chinese children 36 . Similarly, our study suggested that CDKAL1 SNPs are important predictors of the MUHNW phenotype.…”

Section: Discussionmentioning

confidence: 99%

Understanding the genetic architecture of the metabolically unhealthy normal weight and metabolically healthy obese phenotypes in a Korean population

Park

Song

et al. 2021

Sci Rep

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Understanding the mechanisms underlying the metabolically unhealthy normal weight (MUHNW) and metabolically healthy obese (MHO) phenotypes is important for developing strategies to prevent cardiometabolic diseases. Here, we conducted genome-wide association studies (GWASs) to identify the MUHNW and MHO genetic indices. The study dataset comprised genome-wide single-nucleotide polymorphism genotypes and epidemiological data from 49,915 subjects categorised into four phenotypes—metabolically healthy normal weight (MHNW), MUHNW, MHO, and metabolically unhealthy obese (MUHO). We conducted two GWASs using logistic regression analyses and adjustments for confounding variables (model 1: MHNW versus MUHNW and model 2: MHO versus MUHO). GCKR, ABCB11, CDKAL1, LPL, CDKN2B, NT5C2, APOA5, CETP, and APOC1 were associated with metabolically unhealthy phenotypes among normal weight individuals (model 1). LPL, APOA5, and CETP were associated with metabolically unhealthy phenotypes among obese individuals (model 2). The genes common to both models are related to lipid metabolism (LPL, APOA5, and CETP), and those associated with model 1 are related to insulin or glucose metabolism (GCKR, CDKAL1, and CDKN2B). This study reveals the genetic architecture of the MUHNW and MHO phenotypes in a Korean population-based cohort. These findings could help identify individuals at a high metabolic risk in normal weight and obese populations and provide potential novel targets for the management of metabolically unhealthy phenotypes.

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“…Moreover, our data have found that the T2DM susceptibility gene CDKAL1 rs7754840 polymorphism significantly influenced waist and waist-to-hip ratio in FDSP, and waist length and waist-to hip ratio in FDSP with CDKAL1 rs7754840 C/C genotype was significantly larger than that in FDSP with G allele (Figure 2). A recent study also indicated that the risk allele of CDKAL1 rs7754840 polymorphism was closely correlated with increased waist circumference in Chinese Han patients with obesity and T2DM (Kang et al, 2020).…”

Section: Discussionmentioning

confidence: 92%

The type 2 diabetes mellitus susceptibility gene CDKAL1 polymorphism is associated with depressive symptom in first‐episode drug‐naive schizophrenic patients

Xiong

Chen

Zhu

et al. 2021

Human Psychopharmacology

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Background: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1).Objective: To examine whether this polymorphism was involved in the susceptibility in first-episode drug-naive schizophrenic patients (FDSP), and further influenced their clinical symptoms.Methods: This polymorphism was genotyped in 239 FDSP and 368 healthy controls.The clinical symptoms in FDSP were assessed using the Positive and Negative Syndrome Scale (PANSS) five-factor models.Results: There was no significant difference in the allelic and genotypic frequencies of this polymorphism between two groups (both p > 0.05) after adjusting for covariates. However, the PANSS depressive score significantly differed by genotype in FDSP after adjusting for covariates (F = 5.25, p = 0.006). This significant difference also persisted after Bonferroni correction (p < 0.05). FDSP with C/C genotype had significantly higher PANSS depressive score than those with C/G genotype (p = 0.007) and those with G/G genotype (p = 0.005). Moreover, further stepwise multivariate regression analysis showed the significant association between the rs7754840 polymorphism and PANSS depressive score in FDSP (β = −1.07, t = −2.75, p = 0.007). Conclusions:Our findings demonstrated that although the CDKAL1 rs7754840 polymorphism did not contribute to the susceptibility to FDSP, it might be implicated in depressive symptoms in this patient group.

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Obesity-related loci in TMEM18, CDKAL1 and FAIM2 are associated with obesity and type 2 diabetes in Chinese Han patients

Cited by 16 publications

References 38 publications

Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

Understanding the genetic architecture of the metabolically unhealthy normal weight and metabolically healthy obese phenotypes in a Korean population

The type 2 diabetes mellitus susceptibility gene CDKAL1 polymorphism is associated with depressive symptom in first‐episode drug‐naive schizophrenic patients

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