Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis

The vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators, is crucial to calcitriol signalling. VDR is regulated by genetic and environmental factors and it is hypothesised that the response to vitamin D supplementation could be modulated by genetic variants in the VDR gene. The best studied polymorphisms in the VDR gene are Apal (rs7975232), BsmI (rs1544410), Taql (rs731236) and Fokl (rs10735810). We conducted a systematic review and meta-analysis to evaluate the response to vitamin D supplementation according to the BsmI, TaqI, ApaI and FokI polymorphisms. We included studies that analysed the relationship between the response to vitamin D supplementation and the genotypic distribution of these polymorphisms. We included eight studies that enrolled 1038 subjects. The results showed no significant association with the BsmI and ApaI polymorphisms (p = 0.081 and p = 0.63) and that the variant allele (Tt+tt) of the TaqI polymorphism and the FF genotype of the FokI variant were associated with a better response to vitamin D supplementation (p = 0.02 and p < 0.001). In conclusion, the TaqI and FokI polymorphisms could play a role in the modulation of the response to vitamin D supplementation, as they are associated with a better response to supplementation.

A Review of Febrile Seizures: Recent Advances in Understanding of Febrile Seizure Pathophysiology and Commonly Implicated Viral Triggers

Febrile seizures are one of the commonest presentations in young children, with a 2–5% incidence in Western countries. Though they are generally benign, with rare long-term sequelae, there is much to be learned about their pathophysiology and risk factors. Febrile seizures are propagated by a variety of genetic and environmental factors, including viruses and vaccines. These factors must be taken into consideration by a clinician aiming to assess, diagnose and treat a child presenting with fevers and seizures, as well as to explain the sequelae of the febrile seizures to the concerned parents of the child. Our article provides an overview of this common childhood condition, outlining both the underlying mechanisms and the appropriate clinical approach to a child presenting with febrile seizures.

Fruit ripening: dynamics and integrated analysis of carotenoids and anthocyanins

Background Fruits are vital food resources as they are loaded with bioactive compounds varying with different stages of ripening. As the fruit ripens, a dynamic color change is observed from green to yellow to red due to the biosynthesis of pigments like chlorophyll, carotenoids, and anthocyanins. Apart from making the fruit attractive and being a visual indicator of the ripening status, pigments add value to a ripened fruit by making them a source of nutraceuticals and industrial products. As the fruit matures, it undergoes biochemical changes which alter the pigment composition of fruits. Results The synthesis, degradation and retention pathways of fruit pigments are mediated by hormonal, genetic, and environmental factors. Manipulation of the underlying regulatory mechanisms during fruit ripening suggests ways to enhance the desired pigments in fruits by biotechnological interventions. Here we report, in-depth insight into the dynamics of a pigment change in ripening and the regulatory mechanisms in action. Conclusions This review emphasizes the role of pigments as an asset to a ripened fruit as they augment the nutritive value, antioxidant levels and the net carbon gain of fruits; pigments are a source for fruit biofortification have tremendous industrial value along with being a tool to predict the harvest. This report will be of great utility to the harvesters, traders, consumers, and natural product divisions to extract the leading nutraceutical and industrial potential of preferred pigments biosynthesized at different fruit ripening stages.

Genetic basis and dual adaptive role of floral pigmentation in sunflowers

Variation in floral displays, both between and within species, has been long known to be shaped by the mutualistic interactions that plants establish with their pollinators. However, increasing evidence suggests that abiotic selection pressures influence floral diversity as well. Here, we analyse the genetic and environmental factors that underlie patterns of floral pigmentation in wild sunflowers. While sunflower inflorescences appear invariably yellow to the human eye, they display extreme diversity for patterns of ultraviolet pigmentation, which are visible to most pollinators. We show that this diversity is largely controlled by cis-regulatory variation affecting a single MYB transcription factor, HaMYB111, through accumulation of ultraviolet (UV)-absorbing flavonol glycosides in ligules (the ‘petals’ of sunflower inflorescences). Different patterns of ultraviolet pigments in flowers are strongly correlated with pollinator preferences. Furthermore, variation for floral ultraviolet patterns is associated with environmental variables, especially relative humidity, across populations of wild sunflowers. Ligules with larger ultraviolet patterns, which are found in drier environments, show increased resistance to desiccation, suggesting a role in reducing water loss. The dual role of floral UV patterns in pollinator attraction and abiotic response reveals the complex adaptive balance underlying the evolution of floral traits.

Epigenetics and Beyond: Targeting Histone Methylation to Treat Type 2 Diabetes Mellitus

Diabetes mellitus is a global public health challenge with high morbidity. Type 2 diabetes mellitus (T2DM) accounts for 90% of the global prevalence of diabetes. T2DM is featured by a combination of defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. However, the pathogenesis of this disease is complicated by genetic and environmental factors, which needs further study. Numerous studies have demonstrated an epigenetic influence on the course of this disease via altering the expression of downstream diabetes-related proteins. Further studies in the field of epigenetics can help to elucidate the mechanisms and identify appropriate treatments. Histone methylation is defined as a common histone mark by adding a methyl group (-CH3) onto a lysine or arginine residue, which can alter the expression of downstream proteins and affect cellular processes. Thus, in tthis study will discuss types and functions of histone methylation and its role in T2DM wilsed. We will review the involvement of histone methyltransferases and histone demethylases in the progression of T2DM and analyze epigenetic-based therapies. We will also discuss the potential application of histone methylation modification as targets for the treatment of T2DM.

Child Maltreatment and Substance Use: A Behavior Genetic Analysis

Child maltreatment is a pervasive social problem often perpetuated by family members and is related to a wide array of negative life outcomes. Although substance use is an outcome commonly associated with experiences of child maltreatment, not all individuals who experience maltreatment struggle with such issues. Many individuals can positively adapt to experiences of maltreatment based on levels of resilience and susceptibility. Research suggests that genetic differences may partly explain why negative outcomes develop for some, but not for others. Few studies have examined the extent to which genetic and environmental factors influence the longitudinal association between child maltreatment and varying forms of substance use, leaving a fundamental gap in our current understanding of this association. The current study aims to address this gap by analyzing a sample of twins from the National Longitudinal Study of Adolescent to Adult Health (Add Health). Findings from a series of univariate and bivariate biometric models reveal that the longitudinal associations between maltreatment, cigarette use, and marijuana use are accounted for by additive genetic and nonshared environmental factors. Moreover, the magnitude of the contribution varies across unique subgroups of cigarette and marijuana use. Directions for future research and theoretical implications are discussed.

Hypothesis-free detection of gene-interaction effects on biomarker concentration in UK Biobank using variance prioritisation

Blood biomarkers include disease intervention targets that may interact with genetic and environmental factors resulting in subgroups of individuals who respond differently to treatment. Such interactions may be observed in genetic effects on trait variance. Variance prioritisation is an approach to identify genetic loci with interaction effects by estimating their association with trait variance, even where the modifier is unknown or unmeasured. Here, we develop and evaluate a regression-based Brown-Forsythe test and variance effect estimate to detect such interactions. We provide scalable open-source software (varGWAS) for genome-wide association analysis of SNP-variance effects (https://github.com/MRCIEU/varGWAS) and apply our software to 30 blood biomarkers in UK Biobank. We find 468 variance quantitative trait loci across 24 biomarkers and follow up findings to detect 82 gene-environment and six gene-gene interactions independent of strong scale or phantom effects. Our results replicate existing findings and identify novel epistatic effects of TREH rs12225548 x FUT2 rs281379 and TREH rs12225548 x ABO rs635634 on alkaline phosphatase and ZNF827 rs4835265 x NEDD4L rs4503880 on gamma glutamyltransferase. These data could be used to discover possible subgroup effects for a given biomarker during preclinical drug development.

Advances of Genomic Medicine in Psoriatic Arthritis

Psoriatic arthritis (PsA) is a common type of inflammatory arthritis found in up to 40% of patients with psoriasis. Although early diagnosis is important for reducing the risk of irreversible structural damage, there are no adequate screening tools for this purpose, and there are no clear markers of predisposition to the disease. Much evidence indicates that PsA disorder is complex and heterogeneous, where genetic and environmental factors converge to trigger inflammatory events and the development of the disease. Nevertheless, the etiologic events that underlie PsA are complex and not completely understood. In this review, we describe the existing data in PsA in order to highlight the need for further research in this disease to progress in the knowledge of its pathobiology and to obtain early diagnosis tools for these patients.