Research

16 pages, 852 KiB

Open AccessArticle

Association of NAFLD with FGF21 Polygenic Hazard Score, and Its Interaction with Protein Intake Level in Korean Adults

by Hae Jin Lee, Jinyoung Shon and Yoon Jung Park

Nutrients 2023, 15(10), 2385; https://doi.org/10.3390/nu15102385 - 19 May 2023

Cited by 1 | Viewed by 1369

Fibroblast growth factor 21 (FGF21) is a hormone that participates in the regulation of energy homeostasis and is induced by dietary protein restriction. Preclinical studies have suggested that FGF21 induction exerts a protective effect against non-alcoholic fatty liver disease (NAFLD), while human studies [...] Read more.

Fibroblast growth factor 21 (FGF21) is a hormone that participates in the regulation of energy homeostasis and is induced by dietary protein restriction. Preclinical studies have suggested that FGF21 induction exerts a protective effect against non-alcoholic fatty liver disease (NAFLD), while human studies have revealed elevated levels of and potential resistance to FGF21 in patients with NAFLD. However, whether the FGF21 pathway also contributes to NAFLD risk at the genetic level remains uncertain. A few attempts to investigate the impact of individual genetic variants at the loci encoding FGF21 and its receptors on NAFLD risk have failed to establish a clear association due to a limited effect size. Therefore, this study aimed to (1) develop a polygenic hazard score (PHS) for FGF21-related loci that are associated with NAFLD risk and (2) investigate the effect of its interaction with protein intake level on NAFLD risk. Data on 3501 participants of the Korean Genome Epidemiology Study (Ansan–Ansung) were analyzed. Eight single-nucleotide polymorphisms of fibroblast growth factor receptors and beta-klotho were selected for PHS determination using forward stepwise analysis. The association between the PHS and NAFLD was validated (p-trend: 0.0171 for men and <0.0001 for women). Moreover, the association was significantly modulated by the protein intake level in all participants as well as women (p-interaction = 0.0189 and 0.0131, respectively) but not in men. In particular, the women with the lowest PHS values and a protein intake lower than the recommended nutrient intake (RNI) exhibited a greater NAFLD risk (HR = 2.021, p-trend = 0.0016) than those with an intake equal to or greater than the RNI; however, those with higher PHS values had a high risk, regardless of protein intake level. These findings demonstrate the contribution of FGF21-related genetic variants and restricted protein intake to NAFLD incidence. Full article

(This article belongs to the Special Issue Nutrigenetics in Disease Prevention: Mechanistic Pathways and Risk Biomarkers)

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13 pages, 577 KiB

Open AccessArticle

Association between Single Nucleotide Polymorphisms Related to Vitamin D Metabolism and the Risk of Developing Asthma

by Susana Rojo-Tolosa, Laura Elena Pineda-Lancheros, José María Gálvez-Navas, José Antonio Sánchez-Martínez, María Victoria González-Gutiérrez, Andrea Fernández-Alonso, Concepción Morales-García, Alberto Jiménez-Morales and Cristina Pérez-Ramírez

Nutrients 2023, 15(4), 823; https://doi.org/10.3390/nu15040823 - 05 Feb 2023

Cited by 4 | Viewed by 3285

Abstract

Asthma is a chronic non-communicable disease that affects all age groups. The main challenge this condition poses is its heterogeneity. The role of vitamin D in asthma has aroused great interest, correlating low vitamin D levels and polymorphisms in the genes involved in [...] Read more.

Asthma is a chronic non-communicable disease that affects all age groups. The main challenge this condition poses is its heterogeneity. The role of vitamin D in asthma has aroused great interest, correlating low vitamin D levels and polymorphisms in the genes involved in its metabolic pathway with the risk of asthma. The aim of this study was to evaluate the influence of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolism on the susceptibility to asthma. An observational case-control study was performed, including 221 patients with asthma and 442 controls of Caucasian origin from southern Spain. The SNPs CYP24A1 (rs6068816, rs4809957), CYP27B1 (rs10877012, rs4646536, rs703842, rs3782130), GC (rs7041), CYP2R1 (rs10741657) and VDR (ApaI, BsmI, FokI, Cdx2, TaqI) were analyzed by real-time PCR, using TaqMan probes. The logistic regression model adjusted for body mass index revealed that in the genotype model, carriers of the Cdx2 rs11568820-AA genotype were associated with a higher risk of developing asthma (p = 0.005; OR = 2.73; 95% CI = 1.36–5.67; AA vs. GG). This association was maintained in the recessive model (p = 0.004). The haplotype analysis revealed an association between the ACTATGG haplotype and higher risk of asthma for the rs1544410, rs7975232, rs731236, rs4646536, rs703842, rs3782130 and rs10877012 genetic polymorphisms (p = 0.039). The other SNPs showed no effect on risk of developing asthma. The Cdx2 polymorphism was significantly associated with the susceptibility of asthma and could substantially act as a predictive biomarker of the disease. Full article

(This article belongs to the Special Issue Nutrigenetics in Disease Prevention: Mechanistic Pathways and Risk Biomarkers)

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9 pages, 284 KiB

Open AccessArticle

Drinking Habits and Physical Activity Interact and Attenuate Obesity Predisposition of TMEM18 Polymorphisms Carriers

by Danyel Chermon and Ruth Birk

Nutrients 2023, 15(2), 266; https://doi.org/10.3390/nu15020266 - 04 Jan 2023

Cited by 1 | Viewed by 1744

Abstract

The transmembrane protein 18 (TMEM18) gene plays a central and peripheral role in weight regulation. TMEM18 genetic polymorphisms have been identified as an important risk factor for obesity, depending on ethnic population and age. This research aimed to study the association [...] Read more.

The transmembrane protein 18 (TMEM18) gene plays a central and peripheral role in weight regulation. TMEM18 genetic polymorphisms have been identified as an important risk factor for obesity, depending on ethnic population and age. This research aimed to study the association of common TMEM18 polymorphisms with obesity and their interactions with modifiable factors, namely drinking habits (sugar-sweetened beverages (SSBs), flavored water and wine) and physical activity (PA) in the Israeli population. Adults (n = 3089) were analyzed for common TMEM18 polymorphisms and lifestyle and nutrition habits were obtained from questionnaires using adjusted (age, sex) binary logistic regression models. TMEM18 rs939583 and rs1879523 were significantly associated with increased obesity risk (OR = 1.35, 95% CI (1.17–1.57) and OR = 1.66, 95% CI (1.29–2.15), respectively). TMEM18 rs939583 interacted with consumption of 1–3 weekly glasses of wine and PA to attenuate obesity risk (OR = 0.82 95% CI (0.74–0.9; p < 0.001) and OR = 0.74 95% CI (0.68–0.8), respectively), while physical inactivity, SSBs and flavored water consumption significantly enhanced obesity risk (OR = 1.54 95% CI (1.41–1.67), OR = 1.31 95% CI (1.14–1.51) and OR = 1.35 95% CI (1.13–1.62), respectively). PA duration was significantly associated with a lower BMI for rs939583 risk carriers, with a PA cutoff of >30 min/week (p = 0.005) and >90 min/week (p = 0.01). Common TMEM18 SNPs were significantly linked with adult obesity risk and interacted with modifiable lifestyle factors. Full article

(This article belongs to the Special Issue Nutrigenetics in Disease Prevention: Mechanistic Pathways and Risk Biomarkers)

13 pages, 537 KiB

Open AccessArticle

Effect of Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway on Susceptibility to Non-Small-Cell Lung Cancer

by Laura Elena Pineda Lancheros, Susana Rojo Tolosa, José María Gálvez Navas, Fernando Martínez Martínez, Almudena Sánchez Martín, Alberto Jiménez Morales and Cristina Pérez Ramírez

Nutrients 2022, 14(21), 4668; https://doi.org/10.3390/nu14214668 - 04 Nov 2022

Cited by 5 | Viewed by 1660

Abstract

The pathogenesis of non-small-cell lung cancer (NSCLC) is complex, since many risk factors have been identified. Recent research indicates that polymorphisms in the metabolic pathway of vitamin D may be involved in both risk and survival of the disease. The objective of this [...] Read more.

The pathogenesis of non-small-cell lung cancer (NSCLC) is complex, since many risk factors have been identified. Recent research indicates that polymorphisms in the metabolic pathway of vitamin D may be involved in both risk and survival of the disease. The objective of this study is to assess the effect of 13 genetic polymorphisms involved in the vitamin D metabolic pathway on the risk of suffering from NSCLC. We conducted an observational case-control study, which included 204 patients with NSCLC and 408 controls, of Caucasian origin, from southern Spain. The CYP27B1 (rs4646536, rs3782130, rs703842, rs10877012), CYP2R1 (rs10741657), GC (rs7041), CYP24A1, and VDR (BsmI, Cdx-2, FokI, ApaI, TaqI) gene polymorphisms were analyzed by real-time polymerase chain reaction. The logistic regression model, adjusted for smoking and family history of cancer, revealed that in the genotypic model, carriers of the VDR BsmI rs1544410-AA genotype were associated with a lower risk of developing NSCLC compared to the GG genotype (p = 0.0377; OR = 0.51; CI_95% = 0.27–0.95; AA vs. GG). This association was maintained in the recessive model (p = 0.0140). Haplotype analysis revealed that the AACATGG and GACATGG haplotypes for the rs1544410, rs7975232, rs731236, rs4646536, rs703842, rs3782130, and rs10877012 polymorphisms were associated with a lower risk of NSCLC (p = 0.015 and p = 0.044 respectively). The remaining polymorphisms showed no effect on susceptibility to NSCLC. The BsmI rs1544410 polymorphism was significantly associated with lower risk of NSCLC and could be of considerable value as a predictive biomarker of the disease. Full article

(This article belongs to the Special Issue Nutrigenetics in Disease Prevention: Mechanistic Pathways and Risk Biomarkers)

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13 pages, 613 KiB

Open AccessArticle

Association of CYP2R1 and VDR Polymorphisms with Metabolic Syndrome Components in Non-Diabetic Brazilian Adolescents

by Eduarda Pontes dos Santos Araújo, Severina Carla Vieira da Cunha Lima, Ony Araújo Galdino, Ricardo Fernando Arrais, Karla Simone Costa de Souza and Adriana Augusto de Rezende

Nutrients 2022, 14(21), 4612; https://doi.org/10.3390/nu14214612 - 02 Nov 2022

Cited by 2 | Viewed by 1417

Abstract

Associations between vitamin D deficiency and metabolic syndrome (MS) have been reported; however, the underlying biological mechanisms remain controversial. The aim of this study was to investigate the associations of CYP2R1 and VDR variants with MS and MS components in non-diabetic Brazilian adolescents. [...] Read more.

Associations between vitamin D deficiency and metabolic syndrome (MS) have been reported; however, the underlying biological mechanisms remain controversial. The aim of this study was to investigate the associations of CYP2R1 and VDR variants with MS and MS components in non-diabetic Brazilian adolescents. This cross-sectional study included 174 adolescents who were classified as overweight/obese. Three CYP2R1 variants and four VDR variants were identified by allelic discrimination. The CYP2R1 polymorphisms, rs12794714 (GG genotype) (odds ratio [OR] = 3.54, 95% confidence interval [CI] = 1.24–10.14, p = 0.023) and rs10741657 (recessive model—GG genotype) (OR = 3.90, 95%CI = 1.18–12.92, p = 0.026) were significantly associated with an increased risk of MS and hyperglycemia, respectively. The AG + GG genotype (dominant model) of the rs2060793 CYP2R1 polymorphism was associated with hyperglycemia protection (OR = 0.28, 95%CI = 0.08–0.92, p = 0.037). Furthermore, the CC genotype (recessive model) of the rs7975232 VDR polymorphism was significantly associated with a risk of hypertension (OR = 5.91, 95%CI = 1.91–18.32, p = 0.002). In conclusion, the CYP2R1 rs12794714 polymorphism could be considered a possible new molecular marker for predicting the risk of MS; CYP2R1 rs10741657 polymorphism and VDR rs7975232 polymorphism are associated with an increased risk of diabetes and hypertension in adolescents with overweight/obesity. Full article

(This article belongs to the Special Issue Nutrigenetics in Disease Prevention: Mechanistic Pathways and Risk Biomarkers)

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28 pages, 5965 KiB

Open AccessArticle

Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells

by Kok-Lun Pang, Lian-Chee Foong, Norzana Abd Ghafar, Ima Nirwana Soelaiman, Jia Xian Law, Lek Mun Leong and Kok-Yong Chin

Nutrients 2022, 14(20), 4277; https://doi.org/10.3390/nu14204277 - 13 Oct 2022

Cited by 3 | Viewed by 2047

Abstract

Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human [...] Read more.

Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human chondrosarcoma SW1353 cells. Firstly, the MTT assay was performed to determine the half-maximal inhibitory concentration (IC₅₀) of tocotrienol on SW1353 cells after 24 h treatment. The mode of cell death, cell cycle analysis and microscopic observation of tocotrienol-treated SW1353 cells were then conducted according to the respective IC₅₀ values. Subsequently, RNAs were isolated from tocotrienol-treated cells and subjected to RNA sequencing and transcriptomic analysis. Differentially expressed genes were identified and then verified with a quantitative PCR. The current study demonstrated that AnTT, γ-T3 and δ-T3 induced G1 arrest on SW1353 cells in the early phase of treatment (24 h) which progressed to apoptosis upon 48 h of treatment. Furthermore, tocotrienol-treated SW1353 cells also demonstrated large cytoplasmic vacuolation. The subsequent transcriptomic analysis revealed upregulated signalling pathways in endoplasmic reticulum stress, unfolded protein response, autophagy and transcription upon tocotrienol treatment. In addition, several cell proliferation and cancer-related pathways, such as Hippo signalling pathway and Wnt signalling pathway were also significantly downregulated upon treatment. In conclusion, AnTT, γ-T3 and δ-T3 possess promising anticancer properties against chondrosarcoma cells and further study is required to confirm their effectiveness as adjuvant therapy for chondrosarcoma. Full article

(This article belongs to the Special Issue Nutrigenetics in Disease Prevention: Mechanistic Pathways and Risk Biomarkers)

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13 pages, 604 KiB

Open AccessArticle

FTO Common Obesity SNPs Interact with Actionable Environmental Factors: Physical Activity, Sugar-Sweetened Beverages and Wine Consumption

by Danyel Chermon and Ruth Birk

Nutrients 2022, 14(19), 4202; https://doi.org/10.3390/nu14194202 - 09 Oct 2022

Cited by 5 | Viewed by 2030

Abstract

Genetic background is estimated to play >50% in common obesity etiology. FTO single nucleotide polymorphisms (SNPs) are strongly associated with BMI, typically in European cohorts. We investigated the interaction of common FTO SNPs with actionable environmental factors, namely physical activity, sugar-sweetened beverages (SSB) [...] Read more.

Genetic background is estimated to play >50% in common obesity etiology. FTO single nucleotide polymorphisms (SNPs) are strongly associated with BMI, typically in European cohorts. We investigated the interaction of common FTO SNPs with actionable environmental factors, namely physical activity, sugar-sweetened beverages (SSB) and wine consumption, and verified FTO common SNPs predisposition to obesity in the Israeli population. Adults’ (>18 years old, n = 1720) FTO common SNPs data and lifestyle and nutrition habits questionnaires were analyzed using binary logistic regression models, adjusted for confounding variables (age, sex) assuming dominant, recessive and additive genetic models. Eighteen FTO SNPs were associated with significant increased obesity risk and interacted with physical activity (p < 0.001), wine consumption (p < 0.014) and SSB consumption (p < 0.01). Inactive rs9939609 risk-allele carriers had significantly higher obesity risk compared to their active counterparts (OR = 2.54, 95% CI 1.91–3.39 and OR = 3.77, 95% CI 2.47–5.75; p < 0.001 with 3.1 and 3.5 BMI increment for heterozygotes and homozygotes, respectively). SSB consumption (≥1 serving/day) significantly raised obesity risk and wine consumption (1–3 drinks/weekly) significantly lowered obesity risk for rs9939609 risk-allele carriers (OR = 1.54, 95% CI 1.05–2.27; p = 0.028 and OR = 0.61, 95% CI 0.47–0.79; p < 0.001, respectively). Our findings demonstrate that actionable lifestyle factors modify the common FTO obesity risk in predisposed carriers, and they have personal and public health implications. Full article

(This article belongs to the Special Issue Nutrigenetics in Disease Prevention: Mechanistic Pathways and Risk Biomarkers)

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15 pages, 12182 KiB

Open AccessArticle

miR-222 Is Involved in the Amelioration Effect of Genistein on Dexamethasone-Induced Skeletal Muscle Atrophy

by Mailin Gan, Jianfeng Ma, Jingyun Chen, Lei Chen, Shunhua Zhang, Ye Zhao, Lili Niu, Xuewei Li, Li Zhu and Linyuan Shen

Nutrients 2022, 14(9), 1861; https://doi.org/10.3390/nu14091861 - 29 Apr 2022

Cited by 6 | Viewed by 2248

Abstract

Skeletal muscle atrophy is a complex degenerative disease characterized by decreased skeletal muscle mass, skeletal muscle strength, and function. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for muscle [...] Read more.

Skeletal muscle atrophy is a complex degenerative disease characterized by decreased skeletal muscle mass, skeletal muscle strength, and function. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for muscle atrophy. Previous studies have shown beneficial effects of genistein treatment on muscle mass and muscle atrophy, but the mechanism is not fully understood. Differential co-expression network analysis revealed that miR-222 was upregulated in multiple skeletal muscle atrophy models. Subsequent in vitro (C2C12 myoblasts) and in vivo (C57BL/6 mice) experiments showed that genistein could alleviate dexamethasone-induced muscle atrophy and downregulate the expression of miR-222 in muscle tissue and C2C12 myotubes. The dual-luciferase reporter assay system confirmed that IGF1 is a target gene of miR-222 and is regulated by genistein. In C2C12 myotubes, both dexamethasone and miR-222 overexpression promoted muscle atrophy, however, this function was significantly reduced after genistein treatment. Furthermore, we also observed that both genistein and miR-222 antagomiR could significantly inhibit dexamethasone-induced muscle atrophy in vivo. These results suggest that miR-222 may be involved in the regulation of genistein on muscle atrophy, and genistein and miR-222 may be used to improve muscle health. Full article

(This article belongs to the Special Issue Nutrigenetics in Disease Prevention: Mechanistic Pathways and Risk Biomarkers)

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