Salt-Taste Polymorphism TRPV1-rs8065080 Is Associated with Increased Likelihood of Depression in an Elderly Cohort.

INTRODUCTION: Despite the prevalence of depression and anxiety worldwide, their aetiologies remain unclear, and they can be difficult to diagnose and treat. Changes in salt-taste perception have been found in both conditions. Single-nucleotide polymorphisms (SNPs) in the salt-taste-related gene, TRPV1, have been associated with alterations to salt-taste perception, preference, and sodium consumption. Diet quality is a known modifier of depression and anxiety and recently, sodium intake has been studied in mental health. However, the relationships between salt-taste genetics, depression, anxiety, and these dietary factors are yet to be elucidated. METHODS: Data from the well-characterized cross-sectional Retirement Health and Lifestyle Study (n = 536, ≥65 y) were used to explore the relationships between the salt-taste SNP TRPV1-rs8065080, levels of depression and anxiety (Hospital Anxiety and Depression Scale, HADS), estimated sodium intake, and diet quality in this secondary analysis. Standard least-squares regression and nominal logistic regression modelling were used to compare continuous and categorical variables, respectively, with analyses stratified by sex. RESULTS: Presence of the TRPV1-rs8065080 variant allele (C) was found to increase the likelihood of having depression (HADS) in the total population and in males. The associations remained significant after adjusting for sodium intake, three diet quality indices, and demographic variables, suggesting that TRPV1-rs8065080 genotype is driving the association with depression. DISCUSSION/CONCLUSION: Future studies should explore extra-oral functions of the SNP and salt-taste receptors in the brain and the roles of neurotransmitters common to both depression and salt taste to improve the management of this increasingly prevalent and difficult-to-treat condition.

TRAV26-2 T-Cell Receptor Expression Is Associated With Mucosal Lymphocyte Response to Wheat Proteins in Patients With Functional Dyspepsia.

INTRODUCTION: An association between functional dyspepsia (FD) and wheat-containing foods has been reported in observational studies; however, an adaptive response has not been demonstrated. We examined whether antigens present in wheat could provoke a response from FD duodenal lymphocytes. METHODS: Lamina propria mononuclear cells (LPMCs) were isolated from duodenal biopsies from 50 patients with FD and 23 controls. LPMCs were exposed to gluten (0.2 mg/mL) or gliadin (0.2 mg/mL) for 24 hours. Flow cytometry was performed to phenotype lymphocytes. Quantitative PCR was used to measure the expression of gliadin-associated T-cell receptor alpha variant ( TRAV ) 26-2. RESULTS: In response to gliadin (but not gluten) stimulation, the effector Th2-like population was increased in FD LPMCs compared with that in controls and unstimulated FD LPMCs. Duodenal gene expression of TRAV26- 2 was decreased in patients with FD compared with that in controls. We identified a positive association between gene expression of this T-cell receptor variant and LPMC effector Th17-like cell populations in patients with FD, but not controls after exposure to gluten, but not gliadin. DISCUSSION: Our findings suggest that gliadin exposure provokes a duodenal effector Th2-like response in patients with FD, supporting the notion that food antigens drive responses in some patients. Furthermore, these findings suggest that altered lymphocyte responses to wheat proteins play a role in FD pathogenesis.

Thought Leader Perspectives on the Benefits, Barriers, and Enablers for Routinely Collected Electronic Health Data to Support Professional Development: Qualitative Study.

BACKGROUND: Hospitals routinely collect large amounts of administrative data such as length of stay, 28-day readmissions, and hospital-acquired complications; yet, these data are underused for continuing professional development (CPD). First, these clinical indicators are rarely reviewed outside of existing quality and safety reporting. Second, many medical specialists view their CPD requirements as time-consuming, having minimal impact on practice change and improving patient outcomes. There is an opportunity to build new user interfaces based on these data, designed to support individual and group reflection. Data-informed reflective practice has the potential to generate new insights about performance, bridging the gap between CPD and clinical practice. OBJECTIVE: This study aims to understand why routinely collected administrative data have not yet become widely used to support reflective practice and lifelong learning. METHODS: We conducted semistructured interviews (N=19) with thought leaders from a range of backgrounds, including clinicians, surgeons, chief medical officers, information and communications technology professionals, informaticians, researchers, and leaders from related industries. Interviews were thematically analyzed by 2 independent coders. RESULTS: Respondents identified visibility of outcomes, peer comparison, group reflective discussions, and practice change as potential benefits. The key barriers included legacy technology, distrust with data quality, privacy, data misinterpretation, and team culture. Respondents suggested recruiting local champions for co-design, presenting data for understanding rather than information, coaching by specialty group leaders, and timely reflection linked to CPD as enablers to successful implementation. CONCLUSIONS: Overall, there was consensus among thought leaders, bringing together insights from diverse backgrounds and medical jurisdictions. We found that clinicians are interested in repurposing administrative data for professional development despite concerns with underlying data quality, privacy, legacy technology, and visual presentation. They prefer group reflection led by supportive specialty group leaders, rather than individual reflection. Our findings provide novel insights into the specific benefits, barriers, and benefits of potential reflective practice interfaces based on these data sets. They can inform the design of new models of in-hospital reflection linked to the annual CPD planning-recording-reflection cycle.

Volatile compounds in human breath: critical review and meta-analysis.

Volatile compounds contained in human breath reflect the inner workings of the body. A large number of studies have been published that link individual components of breath to disease, but diagnostic applications remain limited, in part due to inconsistent and conflicting identification of breath biomarkers. New approaches are therefore required to identify effective biomarker targets. Here, volatile organic compounds have been identified in the literature from four metabolically and physiologically distinct diseases and grouped into chemical functional groups (e.g. methylated hydrocarbons or aldehydes; based on known metabolic and enzymatic pathways) to support biomarker discovery and provide new insight on existing data. Using this functional grouping approach, principal component analysis doubled explanatory capacity from 19.1% to 38% relative to single individual compound approaches. Random forest and linear discriminant analysis reveal 93% classification accuracy for cancer. This review and meta-analysis provides insight for future research design by identifying volatile functional groups associated with disease. By incorporating our understanding of the complexities of the human body, along with accounting for variability in methodological and analytical approaches, this work demonstrates that a suite of targeted, functional volatile biomarkers, rather than individual biomarker compounds, will improve accuracy and success in diagnostic research and application.

Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia.

Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identifiable pathology. Psychological stress is a key factor associated with the onset of FD and locally acting hypothalamic-pituitary-adrenal (HPA) axis hormones have been implicated in GI motility and barrier dysfunction. Recent pre-clinical work has identified mechanistic pathways linking corticotropin-releasing hormone (CRH) with the innate epithelial immune protein NLRP6, an inflammasome that has been shown to regulate GI mucus secretion. We recruited twelve FD patients and twelve healthy individuals to examine whether dysregulation of hypothalamic-pituitary adrenal (HPA) axis hormones and altered NLRP6 pathways were evident in the duodenal mucosa. Protein expression was assessed by immunoblot and immunohistochemistry in D2 duodenal biopsies. Plasma HPA axis hormones were assayed by ELISA and enteroid and colorectal cancer cell line cultures were used to verify function. FD patients exhibited reduced duodenal CRH-receptor 2, compared to non-GI disease controls, indicating a dysregulation of duodenal HPA signalling. The loss of CRH-receptor 2 correlated with reduced NLRP6 expression and autophagy function, processes critical for maintaining goblet cell homeostasis. In accordance, duodenal goblet cell numbers and mucin exocytosis was reduced in FD patients compared to controls. In vitro studies demonstrated that CRH could reduce NLRP6 in duodenal spheroids and promote mucus secretion in the HT29-MTX-E12 cell line. In conclusion, FD patients exhibit defects in the NLRP6-autophagy axis with decreased goblet cell function that may drive symptoms of disease. These features correlated with loss of CRH receptor 2 and may be driven by dysregulation of HPA signalling in the duodenum of FD patients.

Factors associated with the development of acute general surgical pathology in medical inpatients.

BACKGROUND: Medical inpatients can develop acute general surgical conditions. However, this is rare. The presence of multiple acute pathologies delays diagnosis and these patients have poorer prognoses. AIM: To determine the incidence, risk factors and prognosis of medical inpatients developing acute general surgical conditions. METHODS: A single-centre retrospective case-control study was conducted over 1 year in the United Kingdom. Medical patients developing acute surgical pathology were identified using the local referral system. For each case, two controls were selected from a pool of medical inpatients receiving no general surgical input during their admission. Patient records were used to collect hospital admission details, demographic and laboratory data. Univariate analysis and multivariable analysis were performed. RESULTS: The study included 42 cases and 84 controls. The incidence of general surgical pathology in medical inpatients was 2.3/1000 admissions/year. In multivariate analysis, risk factors associated with developing general surgical pathology were previous abdominal surgery (odds ratio (OR) =3.68; 95% confidence interval (CI): 1.43 to 9.48; P = 0.007) and doubling from baseline creatinine (OR = 18.9; 95% CI: 2.57 to 139; P = 0.004). Patients with surgical pathology had longer inpatient stays (22.8 vs 9.4 days; P < 0.001) and a higher inpatient mortality (23.8% vs 7.1%; P = 0.011). Development of surgical pathology was strongly associated with mortality (OR = 4.06; 95% CI: 1.36 to 12.1). CONCLUSION: The development of acute surgical pathology in medical inpatients is rare but associated with longer inpatient stays and higher mortality. We have identified risk-factors associated with the development of surgical pathology, which can be used to identify patients at risk of surgical pathology.

Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation.

OBJECTIVE: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation." METHODS: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian cross-sectional study population. Genetic analysis was used to score vitamin D- and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D3 were measured by immunoassay and HPLC, respectively. RESULTS: Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. Three dietary antioxidants (vitamins C, E, and ß-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D3 . CONCLUSION: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.

Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia.

Background: Functional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD. Objective: This study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology. Methods: We identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls. Results: There was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 ± 16.11, 19.84 ± 15.51, p=0.038), central memory (23.75 ± 18.97, 37.52 ± 17.51, p=0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p=0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p=0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p=0.027) subsets. Peripheral T cell populations were unchanged between FD and control. Conclusion: Our findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.

Bitter and sweet taste perception: relationships to self-reported oral hygiene habits and oral health status in a survey of Australian adults.

BACKGROUND: Oral health, an essential part of general health and well-being, is influenced by multiple factors, including oral hygiene habits and dietary factors. Dietary preferences are influenced by variation in taste perceptions and threshold tasting. Polymorphisms in specific genes for sweet and bitter taste receptors and bitter taste perception have been associated with dental caries. However, taste is complex with multiple receptors, each with multiple potential polymorphisms contributing to taste perception as well as social, cultural, and environmental influences. Additionally, these association studies have been conducted in restricted cohorts (e.g., children only). Furthermore, outcomes have been limited to dental caries and studies between taste perception and oral hygiene habits have not been completed. METHODS: A cross-sectional online survey was conducted to investigate the relationships between bitter and sweet taste perception (liking and intensity of index food items), self-reported oral hygiene habits and oral health (n = 518). RESULTS: Higher mean intensity scores for bitter (16-21%) and sweet (< 5%-60%) were seen with higher frequencies of oral hygiene habits (brushing, use of mouthwash, chewing gum and tongue cleaning). Lower mean bitter liking scores (18-21%) were seen with higher frequencies of oral hygiene habits (brushing, mouthwash use, floss use and chewing gum). Sweet liking scores varied by reported frequency of mouthwash use and flossing only, with mixed patterns of variance. Mean bitter and sweet intensity perception scores varied with the number of dental caries ((13-20% higher in those with 3 or more caries, compared to none). CONCLUSIONS: While there were numerous relationships identified between liking and perception of sweet and bitter and oral health outcomes, the magnitude and direction of associations varied by outcome. The direction of the associations cannot be inferred due to the cross-sectional nature of the study. The demonstrated relationships justify further future investigations, which could help better understand if taste liking and perception is impacted by oral hygiene and health, or vice versa. This could be important in understanding the causation and progression of oral health diseases or the development of novel therapeutics for oral health.

Sour Taste SNP KCNJ2-rs236514 and Differences in Nutrient Intakes and Metabolic Health Markers in the Elderly.

Single nucleotide polymorphisms (SNPs) in taste receptors influence dietary choices that contribute to health and quality of life. Individual differences in sour taste perception and preference have been linked to heritable genetics, yet the impact of sour taste receptor SNPs on sour taste is under-researched, and studies on sour taste SNP associations to diet and health are lacking. Therefore, this study explored the relationships between the sour taste SNP KCNJ2-rs236514 and estimated macronutrient, vitamin and mineral intakes, and markers of metabolic health. Associations were explored in 523 participants aged 65 years and older with data analysed using standard least squares and nominal logistic regression modelling with post hoc student's t-tests and Tukey's HSD. Associations were found between the presence of the KCNJ2-rs236514 variant allele (A) and lower intakes of energy, total fat, monounsaturated fat and saturated fat. The lower fat intakes were significant in female carriers of the variant allele (A), along with lower water intake. Lower retinol, riboflavin, folate, calcium and sodium intakes were found in the KCNJ2-A allele carriers. In females, the variant allele was associated with lower sodium intake before and after Bonferroni adjustment. Higher body mass index, waist and waist-to-hip ratio measures were found in males carrying the variant allele. Lower levels of liver function biomarkers were associated with the presence of the KCNJ2-A allele. Overall and in males, the variant's association to lower gamma-glutamyl transferase (GGT) levels remained significant after Bonferroni adjustments. These novel findings suggest the sour taste SNP, KCNJ2-rs236514, may be modifying macronutrient, vitamin and mineral intakes, and markers of metabolic health. Research on the extra-oral functions of this SNP may improve health outcomes for those with overweight, obesity and liver disease.

A Rapid Review of Prescribing Education Interventions.

INTRODUCTION: Many studies conducted on the causes and nature of prescribing errors have highlighted the inadequacy of teaching and training of prescribers. Subsequently, a rapid review was undertaken to update on the nature and effectiveness of educational interventions aimed at improving the prescribing skills and competencies. METHODS: Twenty-two studies taking place between 2009 and 2019 were identified across nine databases. RESULTS AND DISCUSSION: This review reinforced the importance of the WHO Guide to Good Prescribing to prescribing curriculum design as well as the effectiveness of small group teaching. However, it also highlighted the lack of innovation in prescribing education and lack of longitudinal follow-up regarding the effectiveness of prescribing education interventions.

Association between Sour Taste SNP KCNJ2-rs236514, Diet Quality and Mild Cognitive Impairment in an Elderly Cohort.

Differences in sour-taste thresholds have been identified in cognition-related diseases. Diet is a modulator of cognitive health, and taste perception influences dietary preferences and habits. Heritable genetics and polymorphisms in the KCNJ2 gene involved in the transduction of sour taste have been linked to variations in sour taste and non-gustatory functions. However, relationships between sour taste genetics, mild cognitive impairment, and diet quality are yet to be elucidated. This study investigated the associations between the presence of the KCNJ2-rs236514 variant (A) allele, diet quality indices, and mild cognitive impairment evaluated by the Mini-Mental State Examination (MMSE), in a secondary cross-sectional analysis of data from the Retirement Health & Lifestyle Study. Data from 524 elderly Australians (≥65y) were analyzed, using standard least squares regression and nominal logistic regression modeling, with demographic adjustments applied. Results showed that the presence of the KCNJ2-A allele is associated with increased proportions of participants scoring in the range indicative of mild or more severe cognitive impairment (MMSE score of ≤26) in the total cohort, and males. These associations remained statistically significant after adjusting for age, sex, and diet quality indices. The absence of association between the KCNJ2-A allele and cognitive impairment in women may be related to their higher diet quality scores in all indices. The potential link between sour taste genotype and cognitive impairment scores may be due to both oral and extra-oral functions of sour taste receptors. Further studies are required on the role and relationship of neurotransmitters, sour taste genotypes and sour taste receptors in the brain, and dietary implications, to identify potential risk groups or avenues for therapeutic or prophylactic interventions.

Genetic Variation in the Bitter Receptors Responsible for Epicatechin Detection Are Associated with BMI in an Elderly Cohort.

Globally, more than one-third of adults are overweight. Overweight and obesity are complex and multifaceted conditions, associated with an increased risk of chronic illness and early mortality. While there are known risk factors, these alone do not fully explain the varying outcomes between individuals. Recently, taste receptors have been proposed to have a role in the risk for obesity. These receptors are expressed throughout the gastrointestinal tract. In this system, they may be involved in modulating dietary intake and metabolic processes. The taste 2 family of receptors (T2Rs) detects bitter compounds. Receptors T2R4 and T2R5 detect (-)-epicatechin (epicatechin), an antioxidant polyphenol, which may have protective effects against obesity. However, the potential role for taste receptors in this association has not been explored. This study assessed whether polymorphisms in TAS2R4 (rs2233998 and rs2234001) and TAS2R5 (rs2227264) were associated with body mass index (BMI). Genotyping (Taqman qPCR assays) was performed on DNA extracted from blood samples (n = 563) from an elderly cohort. Homozygosity for the minor allele of all polymorphisms was significantly associated with a lower BMI in males. The TAS2R4-rs2233998 CC genotype, the TAS2R4-rs2234001 CC genotype and the TAS2R5-rs2227264 TT genotype were associated with lower BMI (2.1, 2.1 and 2.2 units; p = 0.002, 0.003 and 0.001, respectively). Epicatechin intake was not associated with BMI and genotype was not associated with epicatechin intake. This suggests that the association between TAS2R genotype and elevated BMI risk occurs through altered extra-oral responses and not directly via altered epicatechin intake.

What makes a model prescriber? A documentary analysis.

INTRODUCTION: In recent years, the authority to prescribe medications in healthcare has expanded to include pharmacists, nurses and Allied Healthcare Professionals. Subsequently, the quantity of guidelines describing appropriate prescribing practice has increased. Despite this, the literature notes a lack of consensus regarding the overall qualities of a good prescriber. The aim of this study was to attempt to define what makes a model prescriber in practice, regardless of professional background. METHODS: A documentary analysis of UK-based and international prescribing practice guidelines was performed. Data analysis was conducted through a constructivist grounded theory approach to enable concepts to be identified from the data itself without the use of pre-defined categories. RESULTS: A total of 13 guideline documents were analysed. Overall, four core categories of a model prescriber in practice were identified: Knowledgeable: including that of disease and drug properties; Safe: relating to appropriate drug quantities and treatment-monitoring; Good Communicators: with both patients and colleagues; Contemporary: through enhancing knowledge and skills. CONCLUSIONS: These four categories can serve as a definition of a high-level prescriber and as an additional tool for prescribing educators to evaluate the extent their curriculum develops and assesses the core qualities needed by their students to be high-level prescribers in practice.

The impact of inflammatory bowel disease on sexual health in men: A scoping review.

AIMS AND OBJECTIVES: To review the literature on the impact of inflammatory bowel disease on the sexual health of men and make recommendations for nursing practice and research. BACKGROUND: Inflammatory bowel disease is a chronic condition of the gastrointestinal tract, causing symptoms that may impact upon sexual health. Specialist nurses are well positioned to assess and manage sexual health, but there is a lack of clinical guidance, especially in relation to men. DESIGN: A systematic scoping review following the Arksey and O'Malley (International Journal of Social Research Methodology, 8, 2005, 19) framework reported in line with the PRISMA-ScR checklist (Tricco et al., Annals of Internal Medicine, 169, 2018, 467). METHODS: OVID MEDLINE ALL [R], OVID EMBASE [R], OVID PsychINFO, EBSCO CINAHL Complete, The Cochrane Library and ProQuest were searched. Inclusion and exclusion criteria were applied independently by two reviewers. Data were extracted, charted and summarised from eligible studies. RESULTS: Thirty-one studies met the inclusion criteria. These were synthesised under three categories: mediators, moderators and descriptors of sexual health. Depression, disease activity and surgery were the most commonly cited disease-related factors to affect sexual health in men. The most commonly used assessment tool was The International Index of Erectile Function. Descriptors of function included frequency of intercourse, libido and the ability to maintain a desired sexual role. CONCLUSIONS: The effect of inflammatory bowel disease on sexual health in men involves a complex interaction of physical and psychosocial factors. Researchers must explore areas outside of erectile function to understand how the disease impacts sexuality, sexual well-being and masculinity. This can be achieved through qualitative exploration of patient, partner and health professional experiences. RELEVANCE TO CLINICAL PRACTICE: A holistic nursing assessment of men with inflammatory bowel disease should include sexual health. Developing understanding of how the disease influences sexual interaction and expression will facilitate support that is relevant, accessible and of value to men living with the disease.

Intense Sweeteners, Taste Receptors and the Gut Microbiome: A Metabolic Health Perspective.

Intense sweeteners (IS) are often marketed as a healthier alternative to sugars, with the potential to aid in combating the worldwide rise of diabetes and obesity. However, their use has been counterintuitively associated with impaired glucose homeostasis, weight gain and altered gut microbiota. The nature of these associations, and the mechanisms responsible, are yet to be fully elucidated. Differences in their interaction with taste receptors may be a potential explanatory factor. Like sugars, IS stimulate sweet taste receptors, but due to their diverse structures, some are also able to stimulate bitter taste receptors. These receptors are expressed in the oral cavity and extra-orally, including throughout the gastrointestinal tract. They are involved in the modulation of appetite, glucose homeostasis and gut motility. Therefore, taste genotypes resulting in functional receptor changes and altered receptor expression levels may be associated with metabolic conditions. IS and taste receptors may both interact with the gastrointestinal microbiome, and their interactions may potentially explain the relationship between IS use, obesity and metabolic outcomes. While these elements are often studied in isolation, the potential interactions remain unexplored. Here, the current evidence of the relationship between IS use, obesity and metabolic outcomes is presented, and the potential roles for interactions with taste receptors and the gastrointestinal microbiota in modulating these relationships are explored.

Independent and Interactive Influences of Environmental UVR, Vitamin D Levels, and Folate Variant MTHFD1-rs2236225 on Homocysteine Levels.

Elevated homocysteine (Hcy) levels are a risk factor for vascular diseases. Recently, increases in ultraviolet radiation (UVR) have been linked to decreased Hcy levels. This relationship may be mediated by the status of UVR-responsive vitamins, vitamin D and folate, and/or genetic variants influencing their levels; however, this has yet to be examined. Therefore, the independent and interactive influences of environmental UVR, vitamin D and folate levels and related genetic variants on Hcy levels were examined in an elderly Australian cohort (n = 619). Red blood cell folate, 25-hydroxyvitamin D (25(OH)D), and plasma Hcy levels were determined, and genotyping for 21 folate and vitamin D-related variants was performed. Erythemal dose rate accumulated over six-weeks (6W-EDR) and four-months (4M-EDR) prior to clinics were calculated as a measure of environmental UVR. Multivariate analyses found interactions between 6W-EDR and 25(OH)D levels (pinteraction = 0.002), and 4M-EDR and MTHFD1-rs2236225 (pinteraction = 0.006) in predicting Hcy levels. The association between 6W-EDR and Hcy levels was found only in subjects within lower 25(OH)D quartiles (<33.26 ng/mL), with the association between 4M-EDR and Hcy occurring only in subjects carrying the MTHFD1-rs2236225 variant. 4M-EDR, 6W-EDR, and MTHFD1-rs2236225 were also independent predictors of Hcy. Findings highlight nutrient-environment and gene-environment interactions that could influence the risk of Hcy-related outcomes.

Salt Taste Genotype, Dietary Habits and Biomarkers of Health: No Associations in an Elderly Cohort.

A small amount of emerging research has observed variations between individual sensitivity, preference and intake of salt in the presence of single nucleotide polymorphisms (SNP) on the genes encoding salt taste receptors. Sodium intake is a significant risk factor for common diseases in elderly populations such as hypertension and cardiovascular disease; however, this does not fully explain the risk. Research into the influence of salt taste genetics on diet quality is yet to be undertaken and current research on indicators of health is limited and mixed in the direction of associations. Therefore, a secondary analysis of data from a well-characterised elderly cohort (the cross-sectional Retirement Health and Lifestyle Study, n = 536) was conducted to explore relationships between the salt taste-related SNP TRPV1-rs8065080 (assessed by Taqman genotyping assay), dietary habits and biomarkers of health. Data were analysed with standard least squares regression modelling and Tukey's HSD post hoc tests. No association was found between the TRPV1-rs8065080 genotype, sodium intake or multiple diet quality indices (assessed by food frequency questionnaire). Sodium-related markers of health including blood pressure and markers of kidney function (urinary creatinine and albumin/creatinine ratio) and general health markers, such as Body Mass Index (BMI), were also not related to TRPV1-rs8065080 genotype. To date, this study is the most comprehensive investigation conducted to determine if the TRPV1-rs8065080 genotype relates to sodium intake and health markers influenced by sodium intake. Although no significant relationships were found, these findings are an important contribution to the limited body of knowledge surround this SNP. In addition to further research across other ages and cultures, the TRPV1-rs8065080 genotype may interact with other ion channels, and so further studies are required to determine if polymorphic variations influence sodium intake, diet and health.

Environmental UVR Levels and Skin Pigmentation Gene Variants Associated with Folate and Homocysteine Levels in an Elderly Cohort.

Ultraviolet radiation (UVR) is a ubiquitous exposure which may contribute to decreased folate levels. Skin pigmentation mediates the biological effect of UVR exposure, but its relationship to folate levels is unexamined. Interactions may exist between UVR and pigmentation genes in determining folate status, which may, in turn, impact homocysteine levels, a potential risk factor for multiple chronic diseases. Therefore, independent and interactive influences of environmental UVR and genetic variants related to skin pigmentation (MC1R-rs1805007, IRF4-rs12203592 and HERC2-rs12913832) on folate (red blood cell (RBC) and serum) and homocysteine levels were examined in an elderly Australian cohort (n = 599). Genotypes were assessed by RT/RFLP-PCR, and UVR exposures were assessed as the accumulated erythemal dose rate accumulated over 4 months (4M-EDR). Multivariate analysis found significant negative associations between 4M-EDR and RBC folate (p < 0.001, ß = -0.19), serum folate (p = 0.045, ß = -0.08) and homocysteine levels (p < 0.001, ß = -0.28). Significant associations between MC1R-rs1805007 and serum folate levels (p = 0.020), and IRF4-rs12203592 and homocysteine levels (p = 0.026) occurred but did not remain significant following corrections with confounders. No interactions between 4M-EDR and pigmentation variants in predicting folate/homocysteine levels were found. UVR levels and skin pigmentation-related variants are potential determinants of folate and homocysteine status, although, associations are mixed and complex, with further studies warranted.

Distribution of variants in multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP24A1, VDR, RXRα and RXRγ) vary between European, East-Asian and Sub-Saharan African-ancestry populations.

BACKGROUND: The frequency of vitamin D-associated gene variants appear to reflect changes in long-term ultraviolet B radiation (UVB) environment, indicating interactions exist between the primary determinant of vitamin D status, UVB exposure and genetic disposition. Such interactions could have health implications, where UVB could modulate the impact of vitamin D genetic variants identified as disease risk factors. However, the current understanding of how vitamin D variants differ between populations from disparate UVB environments is limited, with previous work examining a small pool of variants and restricted populations only. METHODS: Genotypic data for 46 variants within multiple vitamin D-related loci (DHCR7/NADSYN1, GC, CYP2R1, CYP11A1, CYP27A1, CYP24A1, VDR, RXRα and RXRγ) was collated from 60 sample sets (2633 subjects) with European, East Asian and Sub-Saharan African origin via the NCBI 1000 Genomes Browser and ALFRED (Allele Frequency Database), with the aim to examine for patterns in the distribution of vitamin D-associated variants across these geographic areas. RESULTS: The frequency of all examined genetic variants differed between populations of European, East Asian and Sub-Saharan African ancestry. Changes in the distribution of variants in CYP2R1, CYP11A1, CYP24A1, RXRα and RXRγ genes between these populations are novel findings which have not been previously reported. The distribution of several variants reflected changes in the UVB environment of the population's ancestry. However, multiple variants displayed population-specific patterns in frequency that appears not to relate to UVB changes. CONCLUSIONS: The reported population differences in vitamin D-related variants provides insight into the extent by which activity of the vitamin D system can differ between cohorts due to genetic variance, with potential consequences for future dietary recommendations and disease outcomes.