OBJECTIVES: COVID-19 caused a global pandemic with millions of deaths. Fat mass and obesity-associated gene (FTO) (alias m6A RNA demethylase) and its functional rs17817449 polymorphism are candidates to influence COVID-19-associated mortality since methylation status of viral nucleic acids is an important factor influencing viral viability. METHODS: We tested a population-based cohort of 5233 subjects (aged 63-87 years in 2020) where 70 persons died from COVID-19 and 394 from other causes during the pandemic period. RESULTS: The frequency of GG homozygotes was higher among those who died from COVID-19 (34%) than among survivors (19%) or deaths from other causes (20%), P <0.005. After multiple adjustments, GG homozygotes had a higher risk of death from COVID-19 with odds ratio = 2.01 (95% confidence interval; 1.19-3.41, P <0.01) compared with carriers of at least one T allele. The FTO polymorphism was not associated with mortality from other causes. CONCLUSIONS: Our results suggest that FTO variability is a significant predictor of COVID-19-associated mortality in Caucasians.

• Keywords
• COVID-19, FTO, Mortality, Polymorphism, SARS-CoV-2,
• MeSH
• Alleles MeSH
• COVID-19 * mortality   genetics   virology   MeSH
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO * genetics   MeSH
• Genetic Predisposition to Disease MeSH
• Polymorphism, Single Nucleotide * MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• SARS-CoV-2 physiology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• FTO protein, human MeSH Browser
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO * MeSH

AIM: To replicate the finding that the polymorphism rs6971091 within the NYD-SP18 gene is associated with body mass index (BMI). METHOD: We analysed data of 29,284 adults (46.2% of males, mean age 58.9 (SD 7.3), mean BMI 28.6 (5.0 kg/m2)) examined within the Health Alcohol and Psychosocial Factors in Eastern Europe study in the Czech Republic, Poland, Lithuania and Russia. RESULTS: BMI did not differ by rs6971091 genotype. In men, the mean BMI (SEs) in GG, GA and AA carriers were 27.8 (0.05), 27.9 (0.06) and 27.9 (0.14) kg/m2, respectively, (p = 0.26); in women, the corresponding values were 29.2 (0.06), 29.1 (0.07) and 29.1 (0.16), p = 0.57. In Czech subjects (n = 6,752), for whom the FTO rs17817449 genotype was available, there was no interaction between the NYD-SP18 and FTO polymorphisms in determination of BMI. Adjustment for age, energy and fat intake and physical activity did not materially change the results. There was no association of the NYD-SP18 genotype with waist-hip ratio. CONCLUSION: This study in a large Slavonic population sample suggests that the rs6971091 variant within the NYD-SP18 gene is not an important determinant of obesity in middle-aged persons.

• MeSH
• Alleles MeSH
• Gene Frequency MeSH
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics   metabolism   MeSH
• Genetic Predisposition to Disease MeSH
• Genetic Association Studies MeSH
• Body Mass Index MeSH
• Nuclear Proteins genetics   metabolism   MeSH
• Polymorphism, Single Nucleotide * MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Overweight blood   genetics   metabolism   MeSH
• Obesity blood   genetics   metabolism   MeSH
• Waist-Hip Ratio MeSH
• Registries MeSH
• Reproducibility of Results MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Geographicals
• Czech Republic MeSH
• Lithuania MeSH
• Poland MeSH
• Russia MeSH
• Names of Substances
• FAM71F1 protein, human MeSH Browser
• FTO protein, human MeSH Browser
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
• Nuclear Proteins 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