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1.
Oral absorption of voriconazole is affected by SLCO2B1 c.*396T>C genetic polymorphism in CYP2C19 poor metabolizers.
Lee, SW, Oh, J, Kim, AH, Ji, SC, Park, SI, Yoon, SH, Chung, JY, Yu, KS, Jang, IJ, Lee, S
The pharmacogenomics journal. 2020;(6):792-800
Abstract
High pharmacokinetic variability of voriconazole is mainly explained by CYP2C19 phenotype, but there are still unknown factors affecting the variability. In this study, the effect of solute carrier organic anion transporter family member 2B1 (SLCO2B1) genotype on the pharmacokinetics (PKs) of voriconazole was evaluated in 12 healthy CYP2C19 poor metabolizers after a single administration of voriconazole 200 mg intravenously and orally. In addition, the influence of CYP3A4 enzyme activity was also explored. The oral absorption of voriconazole was decreased and delayed in the subjects with the SLCO2B1 c.*396T>C variant compared to the subjects with wild type. However, the CYP3A activity markers measured in this study did not show significant association with metabolism of voriconazole. The results suggest that the SLCO2B1 c.*396T>C may be associated with the decreased function of intestinal OATP2B1, and it could contribute to interindividual PK variability of voriconazole.
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2.
Vitamin D Receptor Polymorphisms Associated with Autism Spectrum Disorder.
Guerini, FR, Bolognesi, E, Chiappedi, M, Mensi, MM, Fumagalli, O, Rogantini, C, Zanzottera, M, Ghezzo, A, Zanette, M, Agliardi, C, et al
Autism research : official journal of the International Society for Autism Research. 2020;(5):680-690
Abstract
Vitamin D is endowed with a number of biological properties, including down-regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR); the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (Pc = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (Pc = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (Pc = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele-mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI-, BsmI-, ApaI-, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 × 10-4 ; OR: 0.1, 95% CI: 0.03-0.4) too. Finally, a strong gene-dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (Pc = 0.01) and, particularly, with hyperactivity behavior (Pc = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD- and maternal immune activation- associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. Autism Res 2020, 13: 680-690. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY Vitamin D deficiency and Vitamin D receptor (VDR) polymorphisms are associated with structural and functional brain abnormalities and behavioral disorders. We analyzed the association of VDR gene polymorphisms in a cohort of 100 Italian families with ASD children. A strong correlation between one of the VDR polymorphisms and hyperactivity behavior was evidenced in ASD children. In healthy mothers, the same VDR polymorphism was also correlated with an increased risk of giving birth to children with ASD.
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3.
The impact of genetic polymorphisms on weight regain after successful weight loss.
Thonusin, C, Shinlapawittayatorn, K, Chattipakorn, SC, Chattipakorn, N
The British journal of nutrition. 2020;(8):809-823
Abstract
Obesity is associated with an increased risk of various diseases and mortality. Although nearly 50 % of adults have been reported trying to lose weight, the prevalence of obesity has increased. One factor that hinders weight loss-induced decrease in obesity prevalence is weight regain. Although behavioural, psychological and physiological factors associated with weight regain have been reviewed, the information regarding the relationship between weight regain and genetics has not been previously summarised. In this paper, we comprehensively review the association between genetic polymorphisms and weight regain in adults and children with obesity after weight loss. Based on this information, identification of genetic polymorphism in patients who undergo weight loss intervention might be used to estimate their risks of weight regain. Additionally, the genetic-based risk estimation may be used as a guide for physicians and dietitians to provide each of their patients with the most appropriate strategies for weight loss and weight maintenance.
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4.
Vitamin D receptor genetic polymorphisms and the risk of multiple sclerosis: A systematic review and meta-analysis.
Mohammadi, A, Azarnezhad, A, Khanbabaei, H, Izadpanah, E, Abdollahzadeh, R, Barreto, GE, Sahebkar, A
Steroids. 2020;:108615
Abstract
There are conflicting results regarding the exact effect of the vitamin D receptor (VDR) gene polymorphisms on the susceptibility to multiple sclerosis (MS). Therefore, we aimed to investigate the impact of four major studied VDR gene polymorphisms consisting of ApaI, BsmI, FokI, and TaqI on the risk of MS in the Iranian population. A literature search was performed in various databases to find case-control studies evaluating the association between VDR gene polymorphisms and MS risk in Iran. Data were extracted and odds ratios (OR) with 95% confidence intervals (CI) were calculated. Subgroup analyze was performed to detect potential sources of heterogeneity. A total of 1206 cases and 1402 controls in nine case-control studies were included. ApaI was the only variant which showed statistically significant relation in allelic (OR = 0.54 (95% CI: 0.37-0.79); P = 0.00), homozygote (OR = 3.48 (95% CI: 1.7-6.9); P = 0.00), dominant (OR = 0.56 (95% CI: 0.3-0.79); P = 0.01), and recessive (OR = 0.35 (95% CI: 0.18-0.66); P = 0.00) models. The TaqI polymorphism showed a significant negative association with MS only in the homozygote model (OR = 0.28 (95% CI: 0.08-0.9); P = 0.04). The BsmI polymorphism also showed significant relation in allelic (OR = 0.69 (95% CI: 0.51-0.94); P = 0.01), homozygote (OR = 0.46 (95% CI: 0.25-0.86); P = 0.01), and recessive OR = 0.56 (95% CI: 0.39-0.8); P = 0.00) models after performing sensitivity analysis. FokI polymorphism showed no significant association with MS risk. ApaI and TaqI TT genotype were found contributing to MS susceptibility and BsmI and FokI showed no relation with MS susceptibility in the Iranian population.
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5.
The etiopathogenic and morphological spectrum of anencephaly: a comprehensive review of literature.
Munteanu, O, Cîrstoiu, MM, Filipoiu, FM, Neamţu, MN, Stavarache, I, Georgescu, TA, Bratu, OG, Iorgulescu, G, Bohîlţea, RE
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie. 2020;(2):335-343
Abstract
Anencephaly is a severe malformation of the central nervous system (CNS), being one of the most common types of neural tube defects. It is defined as total or partial absence of the calvarium, with absence of the brain. Anencephaly has an incidence of 1 to 5 in every 1000 births, and the mortality rate is 100% during intrauterine life or within hours or days after birth. The etiology of anencephaly remains unclear, but various maternal-related environmental and genetic risk factors have been reported, which include diabetes, obesity, exposure to different drugs or toxins, genetic polymorphisms and mutations, as well as positive family history for neural tube defects. One of the most important nutritional factors in the development of anencephaly is folate deficiency. Methylenetetrahydrofolate reductase (MTHFR) gene codes the enzyme involved in the intracellular metabolism of folic acid; the 677C-T polymorphism of this gene causes the thermolability of the enzyme and decreased enzymatic activity, which is also dependent of folate plasmatic level. Etiopathogenesis of anencephaly includes several mutations in various other genes, such as: platelet-derived growth factor receptor alpha (PDGFRA), cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1), Vang-like 1 (VANGL1) and Vang-like 2 (VANGL2), the last two being involved in the process of neurulation. Screening tests include maternal serum alpha-fetoprotein level and ultrasound (US) examination. During the first trimester US screening, anencephaly is now detected in all cases, but in order to decrease the complication rate of pregnancy termination, the diagnosis should be established as soon as possible, during the pregnancy confirmation US. We conclude that given that anencephaly is a severe malformation of the CNS, morphological characterization could improve the screening by US that is mandatory in the first trimester in order to plan the best, safe and early management.
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6.
Association of Vitamin D Receptor Gene Polymorphisms With Melanoma Risk: A Meta-analysis and Systematic Review.
Birke, M, Schöpe, J, Wagenpfeil, S, Vogt, T, Reichrath, J
Anticancer research. 2020;(2):583-595
Abstract
BACKGROUND/AIM: Increasing evidence indicates a relevance of the vitamin D endocrine system for pathogenesis of malignant melanoma. We performed a systematic review and meta-analysis to update previous reports that investigated the association between vitamin D receptor (VDR) gene polymorphisms and melanoma risk. MATERIALS AND METHODS A comprehensive literature search (PubMed, ISI Web of Science) identified a total of 14 studies that were eligible for inclusion in our meta-analysis. In the statistical analysis, the ORs and the 95% CIs were calculated for the dominant and recessive models for seven VDR gene polymorphisms, namely rs2228570 (FokI), rs731236 (TaqI), rs1544410 (BsmI), rs4516035 (A-1012G), rs11568820 (Cdx2), rs7975232 (ApaI) and rs739837 (BglI). Results were illustrated in Forest Plots. Publication bias was tested using Funnel Plots and the Egger's test. RESULTS Our meta-analysis showed in the dominant model (Bb + BB vs. bb) a significant association of a 15% risk reduction in malignant melanoma incidence for carriers of the rarer allele B of rs1544410 (Bsml). Notably, the dominant model (Ff + ff vs. FF) of rs2228570 (FokI) demonstrates that carriers of the rarer allele f are 22% more likely to develop malignant melanoma. For rs7975232 (ApaI), there is a 20% higher risk of melanoma for carriers of the rarer a allele (Aa + aa vs. AA). The results of the meta-analysis revealed no significant association between melanoma risk and the other investigated VDR polymorphisms. CONCLUSION The VDR variants FokI, ApaI and BsmI may influence the susceptibility to developing melanoma. These findings support the concept, that the vitamin D endocrine system is of importance for pathogenesis of malignant melanoma.
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7.
Investigations of Associations between Seven Gene Polymorphisms and Gestational Diabetes Mellitus: Evidence From a Meta-Analysis.
Wang, B, Xue, X
Gynecologic and obstetric investigation. 2020;(3):229-236
Abstract
BACKGROUND Associations of polymorphisms in transcription factor 7 like 2 (TCF7L2), tumor necrosis factor-α (TNF-α), vitamin D receptor (VDR), and interleukin-10 with gestational diabetes mellitus (GDM) were already reported by several publications. OBJECTIVES The aim of this meta-analysis was to better clarify associations between these polymorphisms and GDM by combing the results of all relevant publications. METHODS Eligible publications were searched from Pubmed, Embase, WOS, and CNKI. We used Review Manager to combine the results of individual studies. RESULTS Thirty-nine studies were included in this study. Combined results revealed that TCF7L2 rs290487, TCF7L2rs7901695, TCF7L2rs7903146, TCF7L2 rs12255372, TNF-α rs1800629, and VDR FokI rs2228570 polymorphisms were all significantly associated with susceptibility to GDM in the total population. In subgroup analyses, we obtained similar positive findings for rs290487, rs7903146, rs1800629, and rs2228570 polymorphisms in Asians, and positive results were also observed for rs7901695, rs7903146, and rs12255372 polymorphisms in Caucasians. CONCLUSIONS Collectively, this meta-analysis proved that TCF7L2 rs290487, TCF7L2rs7901695, TCF7L2rs7903146, TCF7L2 rs12255372, TNF-α rs1800629, and VDR FokI rs2228570 polymorphisms may confer susceptibility to GDM in certain populations.
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8.
Diverse Associations of Plasma Selenium Concentrations and SELENOP Gene Polymorphism with Metabolic Syndrome and Its Components.
Zhou, L, Luo, C, Yin, J, Zhu, Y, Li, P, Chen, S, Sun, T, Xie, M, Shan, Z, Cao, B, et al
Oxidative medicine and cellular longevity. 2020;:5343014
Abstract
The relationship between selenium and metabolic syndrome (MetS) has been discussed controversially, and limited studies have examined the associations of single nucleotide polymorphisms in selenoproteins genes with MetS. Hence, to examine the associations of plasma selenium concentrations and selenoprotein P rs7579 polymorphism with MetS, a case-control study of 1279 MetS cases and 1279 sex- and age- (±2 years) matched controls was conducted based on the baseline data of the Tongji-Ezhou Cohort study. Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry. MetS was defined using the definition of the Joint Interim Statement, adjusted for the Chinese population. In addition, the rs7579 polymorphism was genotyped by the Agena MassARRAY System. Plasma selenium concentrations in the MetS group were higher than in the control group (93.88 μg/L (83.17-107.41) vs. 92.66 μg/L (82.36-103.53), P < 0.05). Compared with quartile 4 (≥103.53 μg/L), the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) associated with MetS were 0.79 (0.59-1.06) for quartile 1 (<82.36 μg/L), 0.75 (0.56-1.01) for quartile 2 (82.37-92.66 μg/L), and 0.61 (0.45-0.83) for quartile 3 (92.67-103.52 μg/L). The cubic spline analyses revealed a U-shaped association between plasma selenium and MetS, with the lowest risk at around 93.69 μg/L. Moreover, in cubic spline analyses, plasma selenium showed U-shaped associations with central obesity and high blood pressure, positive associations with hypertriglyceridemia and hyperglycemia, and a negative association with low high-density lipoprotein cholesterol. Additionally, both the GA and GA+AA genotype carriers were associated with increased ORs of MetS comparing with the GG genotype carriers. Our findings suggested a U-shaped association between plasma selenium and MetS and diverse associations between plasma selenium and components of MetS. Furthermore, our study found that the A allele of rs7579 was associated with higher odds of MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms.
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9.
Appetite effects of prefrontal stimulation depend on COMT Val158Met polymorphism: A randomized clinical trial.
Fassini, PG, Das, SK, Suen, VMM, Magerowski, G, Marchini, JS, da Silva Junior, WA, Changyu, S, Alonso-Alonso, M
Appetite. 2019;:142-150
Abstract
The regulation of appetite is supported by dopamine-modulated brain circuits. Recent studies have shown that transcranial direct current stimulation (tDCS) aimed at increasing the excitability of the dorsolateral prefrontal cortex can reduce appetite, but the underlying mechanisms remain unknown, and response variability is large. The aim of this study was to determine whether individual differences in Catechol-O-methyl transferase (COMT) Val158Met polymorphism can influence tDCS effects on appetite. Thirty-eight adult women with obesity, classified as carriers or non-carriers of the Met allele, underwent a randomized, double-blind, sham-controlled tDCS intervention involving three phases: Phase I, target engagement (immediate effects of tDCS on working memory performance), Phase II, tDCS only (10 sessions, two weeks), and Phase III, tDCS + hypocaloric diet: (6 sessions, two weeks, 30% energy intake reduction, inpatient). Data were analyzed using linear mixed-effects models and mixed ANCOVA. Appetite was evaluated using visual analogue scales. We found that Met-carriers receiving active tDCS were the only participants who experienced a significant reduction of appetite over time. Conversely, Met non-carriers maintained high levels of appetite during the intervention; this effect was driven by a delayed paradoxical rise in appetite after stimulation. Working memory task performance at phase I correlated with subsequent appetite change in a COMT-dependent manner: speed improvements during the task predicted appetite increase in Met carriers and appetite reduction in Met non-carriers. Our findings suggest that genotype differences impacting dopamine levels influence prefrontal tDCS effects on appetite. This source of variability should be considered in the design of future studies.
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10.
The Research Progress of Host Genes and Tuberculosis Susceptibility.
Cai, L, Li, Z, Guan, X, Cai, K, Wang, L, Liu, J, Tong, Y
Oxidative medicine and cellular longevity. 2019;:9273056
Abstract
BACKGROUND/AIMS: Nucleotide diversity may affect the immune regulation of tuberculosis (TB) patients, leading to the individual susceptibility to TB. In recent years, there are a lot of researches on the association of host genetic factors and TB susceptibility which has attracted increasing attention, and the in-depth study of its mechanism is gradually clear. MATERIALS We made a minireview on the association of many candidate genes with TB based on recent research studies systematically, such as the human leukocyte antigen (HLA) gene, the solute carrier family 11 member 1 (SLC11A1) gene system, the vitamin D receptor (VDR) gene, the mannan-binding lectin (MBL) gene, the nitric oxide synthase 2A (NOS2A) gene, the speckled 110 (SP110) gene, and the P2X7 receptor (P2X7) gene. The discovery of these candidate genes could reveal the pathogenesis of TB comprehensively and is crucial to provide scientific evidence for formulating the related measures of prevention and cure. DISCUSSION The host genes play important roles in the development of TB, and the host genes may become new targets for the prevention and treatment of TB. Effective regulation of host genes may help prevent or even treat TB. CONCLUSION This minireview focuses on the association of host genes with the development of TB, which may supply some clues for future therapies and novel drug targets for TB.