Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population.

BACKGROUND: Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to better understand disease mechanisms. Here, we performed eQTL mapping in subcutaneous (S) and visceral (V) adipose tissue from 106 Greek individuals (Greek Metabolic study, GM) and compared our findings to those from the Genotype-Tissue Expression (GTEx) resource. RESULTS: We identified 1,930 and 1,515 eGenes in S and V respectively, over 13% of which are not observed in GTEx adipose tissue, and that do not arise due to different ancestry. We report additional context-specific regulatory effects in genes of clinical interest (e.g. oncogene ST7) and in genes regulating responses to environmental stimuli (e.g. MIR21, SNX33). We suggest that a fraction of the reported differences across populations is due to environmental effects on gene expression, driving context-specific eQTLs, and suggest that environmental effects can determine the penetrance of disease variants thus shaping disease risk. We report that over half of GM eQTLs colocalize with GWAS SNPs and of these colocalizations 41% are not detected in GTEx. We also highlight the clinical relevance of S adipose tissue by revealing that inflammatory processes are upregulated in individuals with obesity, not only in V, but also in S tissue. CONCLUSIONS: By focusing on an understudied population, our results provide further candidate genes for investigation regarding their role in adipose tissue biology and their contribution to disease risk and pathogenesis.

The iMPROVE Study; Design, Dietary Patterns, and Development of a Lifestyle Index in Overweight and Obese Greek Adults.

BACKGROUND: Dietary and lifestyle habits constitute a significant contributing factor in the formation of anthropometric and biochemical characteristics of overweight and obese populations. The iMPROVE study recruited overweight and obese Greek adults and investigated the effect of gene-diet interactions on weight management when adhering to a six-month, randomized nutritional trial including two hypocaloric diets of different macronutrient content. The present paper displays the design of the intervention and the baseline findings of the participants' dietary habits and their baseline anthropometric and biochemical characteristics. METHODS: Baseline available data for 202 participants were analyzed and patterns were extracted via principal component analysis (PCA) on 69-item Food-Frequency Questionnaires (FFQ). Relationships with indices at baseline were investigated by multivariate linear regressions. A Lifestyle Index of five variables was further constructed. RESULTS: PCA provided 5 dietary patterns. The "Mixed" pattern displayed positive associations with logBMI and logVisceral fat, whereas the "Traditional, vegetarian-alike" pattern was nominally, negatively associated with body and visceral fat, but positively associated with HDL levels. The Lifestyle Index displayed protective effects in the formation of logBMI and logGlucose levels. CONCLUSIONS: Dietary patterns and a Lifestyle Index in overweight and obese, Greek adults highlighted associations between diet, lifestyle, and anthropometric and biochemical indices.

Biomarkers in the field of obesity and its related comorbidities.

INTRODUCTION: The prevalence of obesity has increased dramatically in the last decades both in children and adults and is now considered a major health problem. It is associated with numerous comorbidities such as hypertension, dyslipidemia, diabetes and subsequent cardiovascular disease (CVD). One of the mechanisms that connect obesity with these comorbidities is the secretion of so-called adipocytokines or adipokines by the adipose tissue itself. Most adipokines with pro-inflammatory properties are overproduced with increasing adiposity, whereas some adipokines with anti-inflammatory or insulin-sensitizing properties, like adiponectin, are decreased. This dysregulation of adipokines production may promote obesity-linked metabolic disorders and CVD. Except adipokines a wide complex network of chemicals balances pro-inflammatory and anti-inflammatory effects. AREAS COVERED: In this review, we summarize the role of various adipokines and other chemicals associated with obesity and its related cardiometabolic comorbidities, with a special focus on recent evidence showing their potential role as biomarkers whose expression are indicative of obesity and its complications. EXPERT OPINION: Biomarkers associated with obesity, type 2 diabetes (T2D) and CVD could prove beneficial for early identification, proper treatment and good life assurance. Unfortunately, the complexity of biological pathways interactions is such that further research is necessary before any of these markers could reach an accurate diagnostic value.