Associations between TUBB-WWOX SNPs, their haplotypes, gene-gene, and gene-environment interactions and dyslipidemia

Liu, Chunxiao; Yin, Rong; Shi, Zong-Hu; Zheng, Peng-Fei; Deng, Guo-Xiong; Guan, Yao-Zong; Wei, Bi-Liu

doi:10.18632/aging.202514

Cited by 5 publications

(5 citation statements)

References 51 publications

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“…In mice fed a high-fat diet, the expression of TUBB2A and TUBB6 were significantly increased [ 26 ]. In humans, TUBB was reported to increase the risk of dyslipidemia and predict hypertension [ 27 ]. In the present study, we found that TUBB2B increased the cholesterol level in HCC cell lines, leading to an increase of proliferation and decrease of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1

et al. 2023

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Cholesterol metabolism plays a critical role in the progression of hepatocellular carcinoma (HCC), but it is not clear how cholesterol metabolism is regulated. The tubulin beta class I genes (TUBBs) are associated with the prognosis of many different cancers. To confirm the function of TUBBs in HCC, the Kaplan–Meier method and Cox analyses were performed using TCGA and GSE14520 datasets. A higher expression of TUBB2B is an independent prognostic factor for shorter over survival in HCC patients. Deletion of TUBB2B in hepatocytes inhibits proliferation and promotes tumor cell apoptosis, while over-expression of TUBB2B has the opposite function. This result was confirmed in a mouse xenograft tumor model. Mechanistically, TUBB2B induces the expression of CYP27A1, an enzyme responsible for the conversion of cholesterol to 27-hydroxycholesterol, which leads to the up-regulation of cholesterol and the progression of HCC. In addition, TUBB2B regulates CYP27A1 via human hepatocyte nuclear factor 4alpha (HNF4A). These findings indicated that TUBB2B functions as an oncogene in HCC, and plays a role in promoting cell proliferation and anti-apoptosis through targeting HNF4A/CYP27A1/cholesterol.

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Section: Discussionmentioning

confidence: 99%

TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1

et al. 2023

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“…It is speculated that individuals with the MTMR9 rs2293855 polymorphism would have a greater preference for fatty foods, thus contributing to the occurrence of dyslipidaemia. However, it is important to highlight that genetic mechanisms are influenced by many interactions, including synergistic or contrasting effects between genes on gene expression and environmental factors (Liu et al., 2021). It is already known that individuals with genetic polymorphisms may be more predisposed to the development of dyslipidaemia; however, environmental factors can alter the lipid expression profile (Jha et al., 2019; Wang et al., 2017), explaining why some individuals do not develop the disease, even though they have the genetic predisposition to it, while others, without the presence of the polymorphism, have dyslipidaemia.…”

Section: Discussionmentioning

confidence: 99%

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score

Silva,

Resende,

Louro

et al. 2023

Nutrition Bulletin

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Childhood dyslipidaemia is associated with the occurrence of cardiovascular diseases in adulthood, so evaluating whether an individual has a genetic predisposition to this pathology is of great importance for early action of prevention and treatment. This study aimed to evaluate the association between the FTO (rs9939609), MC4R (rs17782313) and MTMR9 (rs2293855) polymorphisms, the obesity‐related genetic risk score and atherogenic risk in Brazilian children. This is a cross‐sectional study conducted in 544 children aged 4–9 years in the city of Viçosa, Minas Gerais state, Brazil. The single nucleotide polymorphisms rs9939609, rs17782313 and rs2293855, were identified by the system TaqMan SNP genotyping and the obesity‐related genetic risk score was determined. The lipid profile (serum total cholesterol [TC], high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol, triglycerides) was analysed and the atherogenic indices (Castelli I and II indices), atherogenic coefficient (AC), lipoprotein combined index (LCI) and plasma atherogenic index (PAI) were calculated. A semi‐structured questionnaire was applied, obtaining data on the sociodemographic, economic and lifestyle characteristics of the children. Weight and height measurements were performed in all children, and body composition was evaluated by Dual‐Energy X‐ray Absorptiometry (DXA). 55.5% of the sample had dyslipidaemia, while 28.5% of the sample had at least one polymorphism and 2.2% had three polymorphisms. Children with the AG/AA genotypes in the rs2293855 polymorphism had lower HDL cholesterol levels and higher TC/HDL cholesterol, LDL/HDL cholesterol ratios and AC. Those with one or more polymorphisms (rs9939609, rs17782313 and rs2293855) in the genetic risk score had lower HDL cholesterol levels and higher TC/HDL cholesterol ratios, AC, LCI and PAI. In conclusion, the risk allele of the rs2293855 polymorphism and a higher obesity‐related genetic risk score were positively associated with higher atherogenic risk in Brazilian children.

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“…Our study identified family history of dyslipidemia as an independent risk factor for dyslipidemia, which is consistent with several previous studies ( 9 , 28 ). While the exact mechanisms by which family history of dyslipidemia increases the risk of dyslipidemia are not fully understood, it is believed that genetic factors may play a role ( 29 , 30 ). Certain genes have been identified that increase the risk of dyslipidemia, including genes that regulate cholesterol metabolism and lipoprotein synthesis ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

The association of body mass index and its interaction with family history of dyslipidemia towards dyslipidemia in patients with type 2 diabetes: a cross-sectional study in Zhejiang Province, China

Chen

Fang

Zhang

et al. 2023

Front. Public Health

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ObjectivesThis study aimed to investigate the association between body mass index (BMI) and dyslipidemia and to explore the interaction between BMI and family history of dyslipidemia towards dyslipidemia in patients with type 2 diabetes.MethodsThis cross-sectional study was conducted between March and November 2018 in Zhejiang Province, China. A total of 1,756 patients with type 2 diabetes were included, physical examination data, fasting blood samples and face-to-face questionnaire survey data were collected. Restricted cubic spline analysis was used to evaluate the association between BMI and the risk of dyslipidemia. Unconditional multivariable logistic regression was used to estimate the interaction between BMI and family history of dyslipidemia towards dyslipidemia.ResultsThe prevalence of dyslipidemia was 53.7% in the study population. The risk of dyslipidemia elevated with increased BMI value (p for non-linearity <0.05). After adjusting for covariates, individuals with high BMI (≥24 kg/m2) and a family history of dyslipidemia had a 4.50-fold (95% CI: 2.99–6.78) increased risk of dyslipidemia compared to the normal reference group, which was higher than the risk associated with high BMI alone (OR = 1.83, 95% CI: 1.47–2.28) or family history of dyslipidemia alone (OR = 1.79 95% CI: 1.14–2.83). Significant additive interaction between high BMI and a family history of dyslipidemia was detected, with RERI, AP, and SI values of 1.88 (95% CI: 0.17–4.10), 0.42 (95% CI: 0.02–0.62), and 2.16 (95% CI: 1.07–4.37), respectively. However, stratified by status of diabetes control, this additive interaction was only find significant among patients with controlled diabetes.ConclusionBoth high BMI and a family history of dyslipidemia were related with high risk of dyslipidemia. Moreover, there were synergistic interaction between these two factors. Patients with type 2 diabetes who had a family history of dyslipidemia were more susceptible to the negative impact of being overweight or obesity on dyslipidemia.

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Associations between TUBB-WWOX SNPs, their haplotypes, gene-gene, and gene-environment interactions and dyslipidemia

Cited by 5 publications

References 51 publications

TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1

TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score

The association of body mass index and its interaction with family history of dyslipidemia towards dyslipidemia in patients with type 2 diabetes: a cross-sectional study in Zhejiang Province, China

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