Most cited article - PubMed ID 19278366
A common variant in the FTO gene is associated with body mass index in males and postmenopausal females but not in premenopausal females. Czech post-MONICA and 3PMFs studies
Among unique cardiovascular risk factors in women are complications during pregnancy, including miscarriage. Important risk factor is also genetic background. One of powerful candidate genes for cardiovascular disease of atherosclerotic origin (aCVD) is gene for connexin 37 (Cx37) with strong gene-environment interaction including smoking status, that is also strong risk factor for complications in pregnancy including spontaneous abortion (SA). We analyzed association between SA and Cx37 gene polymorphism (1019C>T; Pro319Ser) in 547 fetuses and its potential interaction with smoking status of mothers. Using genetic analyses from women from general population as controls, ORs for T allele, found in our previous studies to be protective against aCVD, were calculated. T allele carriers (fetuses), had OR 0.91 (95 % CI 0.72-1.14) and no interaction with smoking was observed. In conclusion, no significant association between Cx37 polymorphism and SA was observed and no modifying effect of smoking status on this association was detected.
- MeSH
- Biomarkers MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Heterozygote MeSH
- Polymorphism, Single Nucleotide MeSH
- Connexins genetics MeSH
- Smoking MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Fetus MeSH
- Polymorphism, Genetic MeSH
- Gap Junction alpha-4 Protein MeSH
- Risk Factors MeSH
- Abortion, Spontaneous genetics MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Biomarkers MeSH
- Connexins MeSH
In contrast to the decreasing burden related to cardiovascular disease (CVD), the burden related to dysglycemia and adiposity complications is increasing in Czechia, and local drivers must be identified. A comprehensive literature review was performed to evaluate biological, behavioral, and environmental drivers of dysglycemia and abnormal adiposity in Czechia. Additionally, the structure of the Czech healthcare system was described. The prevalence of obesity in men and diabetes in both sexes has been increasing over the past 30 years. Possible reasons include the Eastern European eating pattern, high prevalence of physical inactivity and health illiteracy, education, and income-related health inequalities. Despite the advanced healthcare system based on the compulsory insurance model with free-for-service healthcare and a wide range of health-promoting initiatives, more effective strategies to tackle the adiposity/dysglycemia are needed. In conclusion, the disease burden related to dysglycemia and adiposity in Czechia remains high but is not translated into greater CVD. This discordant relationship likely depends more on other factors, such as improvements in dyslipidemia and hypertension control. A reconceptualization of abnormal adiposity and dysglycemia into a more actionable cardiometabolic-based chronic disease model is needed to improve the approach to these conditions. This review can serve as a platform to investigate causal mechanisms and secure effective management of cardiometabolic-based chronic disease.
- Keywords
- adiposity, cardiometabolic risk, cardiovascular disease, chronic disease, dysglycemia, insulin resistance, nutrition, obesity, type 2 diabetes,
- MeSH
- Adiposity ethnology MeSH
- White People statistics & numerical data MeSH
- Chronic Disease epidemiology ethnology MeSH
- Diabetes Mellitus, Type 2 epidemiology ethnology MeSH
- Diet adverse effects ethnology MeSH
- Health Status Disparities MeSH
- Adult MeSH
- Dyslipidemias epidemiology ethnology MeSH
- Hypertension epidemiology ethnology MeSH
- Cardiometabolic Risk Factors MeSH
- Cardiovascular Diseases epidemiology etiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Metabolic Syndrome epidemiology ethnology MeSH
- Obesity epidemiology ethnology MeSH
- Glucose Intolerance epidemiology ethnology MeSH
- Prediabetic State epidemiology ethnology MeSH
- Prevalence MeSH
- Sedentary Behavior ethnology MeSH
- Social Determinants of Health ethnology MeSH
- Feeding Behavior ethnology MeSH
- Health Literacy MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- Czech Republic epidemiology MeSH
Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), has spread widely around the globe. Significant inter-individual differences have been observed during the course of the infection, which suggests that genetic susceptibility may be a contributing factor. CC chemokine receptor 5 (CCR5), which acts as a co-receptor for the entry of HIV-1 into cells, is promising candidate whose can have an influence on SARS-CoV-2 infection. A genetic mutation known as CCR5Delta32, consisting of a 32-nucleotide deletion, encodes a truncated protein that protects homozygous carriers of the deletion from HIV-1 infection. Similarly, inhibition of CCR5 seems to be protective against COVID-19. In our study, we successfully genotyped 416 first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) for CCR5?32, comparing them with a population based sample of 2,404 subjects. We found the highest number (P=0.03) of CCR5Delta32 carriers in SARS-CoV-2-positive/COVID-19-asympto-matic subjects (23.8 %) and the lowest number in SARS-CoV-2-positive/COVID-19-symptomatic patients (16.7 %), with frequency in the control population in the middle (21.0 %). We conclude that the CCR5?32 I/D polymorphism may have the potential to predict the severity of SARS-CoV-2 infection.
- MeSH
- COVID-19 diagnosis genetics virology MeSH
- Phenotype MeSH
- Gene Frequency MeSH
- Genetic Predisposition to Disease MeSH
- Genetic Association Studies MeSH
- Risk Assessment MeSH
- Humans MeSH
- Protective Factors MeSH
- Receptors, CCR5 genetics MeSH
- Risk Factors MeSH
- Sequence Deletion * MeSH
- Case-Control Studies MeSH
- Severity of Illness Index MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- CCR5 protein, human MeSH Browser
- Receptors, CCR5 MeSH
BACKGROUND: Genome-wide association studies identified the FTO (fat mass and obesity gene) gene as an important determinant of body weight. More recently, the FTO gene was reported to be associated with other outcomes, including major risk factors for chronic kidney disease (CKD). We investigated the role of this gene in the risk of end-stage renal disease (ESRD) caused by CKD. METHODS: We conducted two large population-based case-control studies of ESRD. Study 1 compared 984 haemodialysed patients with ESRD with 2501 participants in the Czech post-MONICA study; Study 2 compared 1188 patients included in a kidney transplantation programme for ESRD with 6681 participants in the Czech HAPIEE study. The frequencies of the FTO rs17817449 single nucleotide polymorphism genotype were compared between cases and controls. RESULTS: The FTO rs17817449 genotype was significantly associated with CKD in both studies (P-values 0.00004 and 0.006, respectively). In the pooled data, the odds ratios of CKD for GG and GT, versus TT genotype, were 1.37 (95% confidence interval 1.20-1.56) and 1.17 (1.05-1.31), respectively (P for trend <0.0001). Among haemodialysed and kidney transplant patients, the onset of ESRD in GG homozygotes was 3.3 (P = 0.012) and 2.5 (P = 0.032) years, respectively, earlier than in TT homozygotes. CONCLUSIONS: These two large independent case-control studies in the general population found robust associations between the FTO rs17817449 polymorphism and the ESRD. The results suggest that the morbidities associated with the FTO gene include CKD.
- MeSH
- Genome-Wide Association Study MeSH
- Kidney Failure, Chronic epidemiology genetics MeSH
- DNA genetics MeSH
- Adult MeSH
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
- Genetic Predisposition to Disease MeSH
- Genotype MeSH
- Body Mass Index MeSH
- Middle Aged MeSH
- Humans MeSH
- Polymerase Chain Reaction MeSH
- Polymorphism, Genetic genetics MeSH
- Proteins genetics MeSH
- Risk Factors MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Age of Onset MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Research Support, N.I.H., Extramural MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- DNA MeSH
- FTO protein, human MeSH Browser
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
- Proteins MeSH
The FTO gene variants are the most important genetic determinants of body weight and obesity known so far, but the mechanism of their effect remains unclear. We have analyzed FTO rs17817449 variant (G>T in first intron) in 6024 adults aged 45-69 years to assess the potential mediating role of diet and physical activity. Diet was assessed by a 140-item food frequency questionnaire. Physical activity was measured by hours spent during a typical week by sport, walking and other activities outside of work requiring heavy and medium physical activity. Basal metabolic rate was calculated according Schofield formula. The FTO variant was significantly associated with body mass index (means in GG, GT and TT carriers were 28.7, 28.2 and 27.8 kg/m(2), p<0.001) and basal metabolic rate (BMR) (means in GG, GT and TT were 1603, 1588 and 1576 kcal per day, respectively, p<0.008) but it was not associated with physical activity, total energy intake or with energy intakes from fat, carbohydrates, proteins or alcohol. Results were essentially similar in men and women and the adjustment for physical activity or dietary energy intake did not reduce the effect of the FTO polymorphism. Means of BMR per kg of body weight was lowest in GG carriers (20.09, 20.21 for GT and 20.30 for TT, p<0.006) and this effect was more pronounced in females. These results suggest that the effect of the FTO rs17817449 variant on BMI in Caucasian adults is not mediated by energy intake or physical activity, but some effect on BMR per kg of body weight is possible.
- MeSH
- Basal Metabolism genetics MeSH
- White People genetics MeSH
- Exercise * MeSH
- Energy Intake genetics MeSH
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
- Body Mass Index MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- Proteins genetics MeSH
- Body Composition genetics MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- FTO protein, human MeSH Browser
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
- Proteins MeSH
- MeSH
- Genome-Wide Association Study MeSH
- Epigenesis, Genetic MeSH
- Ethnicity genetics MeSH
- Gene Frequency genetics MeSH
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
- Genetic Association Studies * MeSH
- Genome, Human genetics MeSH
- Body Mass Index * MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Humans MeSH
- Obesity genetics MeSH
- Proteins genetics MeSH
- Reproducibility of Results MeSH
- Geography MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Letter MeSH
- Comment MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- FTO protein, human MeSH Browser
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
- Proteins MeSH