We tested associations between 13 established genetic variants and type 2 diabetes (T2D) in 1371 study participants from the Volga-Ural region of the Eurasian continent, and evaluated the predictive ability of the model containing polygenic scores for the variants associated with T2D in our dataset, alone and in combination with other risk factors such as age and sex. Using logistic regression analysis, we found associations with T2D for the CCL20 rs6749704 (OR = 1.68, PFDR = 3.40 × 10−5), CCR5 rs333 (OR = 1.99, PFDR = 0.033), ADIPOQ rs17366743 (OR = 3.17, PFDR = 2.64 × 10−4), TCF7L2 rs114758349 (OR = 1.77, PFDR = 9.37 × 10−5), and CCL2 rs1024611 (OR = 1.38, PFDR = 0.033) polymorphisms. We showed that the most informative prognostic model included weighted polygenic scores for these five loci, and non-genetic factors such as age and sex (AUC 85.8%, 95%CI 83.7%–87.8%). Compared to the model containing only non-genetic parameters, adding the polygenic score for the five T2D-associated loci showed improved net reclassification (NRI = 37.62%, 1.39 × 10−6). Inclusion of all 13 tested SNPs to the model with age and sex did not improve the predictive ability compared to the model containing five T2D-associated variants (NRI = −17.86, p = 0.093). The five variants associated with T2D in people from the Volga-Ural region are linked to inflammation (CCR5, CCL2, CCL20) and glucose metabolism regulation (TCF7L, ADIPOQ2). Further studies in independent groups of T2D patients should validate the prognostic value of the model and elucidate the molecular mechanisms of the disease development.
Obesity affects over 700 million people worldwide and its prevalence keeps growing steadily. The problem is particularly relevant due to the increased risk of COVID-19 complications and mortality in obese patients. Obesity prevalence increase is often associated with the influence of environmental and behavioural factors, leading to stigmatization of people with obesity due to beliefs that their problems are caused by poor lifestyle choices. However, hereditary predisposition to obesity has been established, likely polygenic in nature. Morbid obesity can result from rare mutations having a significant effect on energy metabolism and fat deposition, but the majority of patients does not present with monogenic forms. Microbiome low diversity significantly correlates with metabolic disorders (inflammation, insulin resistance), and the success of weight loss (bariatric) surgery. However, data on the long-term consequences of bariatric surgery and changes in the microbiome composition and genetic diversity before and after surgery are currently lacking. In this review, we summarize the results of studies of the genetic characteristics of obesity patients, molecular mechanisms of obesity, contributing to the unfavourable course of coronavirus infection, and the evolution of their microbiome during bariatric surgery, elucidating the mechanisms of disease development and creating opportunities to identify potential new treatment targets and design effective personalized approaches for the diagnosis, management, and prevention of obesity.
The aim of the present study was to investigate the association of COPD and frequent exacerbator COPD phenotype with CRP, CD14, and pro-inflammatory cytokines and their receptors (TNFA, LTA, TNFRSF1A, TNFRSF1B, IL1B, and IL6) genes. It was found that COPD was associated with allele A of the TNFA gene (rs1800629G>A)
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