BACKGROUND This study was carried out to determine the relationship between the common TMEM-18 (rs4854344, G>T) and NYD-SP18 (rs6971091, G>A) gene variants and weight loss after lifestyle interventions (increased physical activity in conjunction with optimal dietary intake) in overweight/obese children/adolescents. MATERIAL AND METHODS We genotyped 684 unrelated, white, non-diabetic children (age 12.7±2.1 years, average BMI at baseline 30.66±4.80 kg/m²). Anthropometric and biochemical examinations were performed before and after 4 weeks of an intensive lifestyle intervention. RESULTS The mean weight loss achieved was 5.20±2.02 kg (P<0.001). NYDSP-18 AA homozygotes had significantly higher abdominal skinfold value before and after the intervention (both, P=0.001). No significant associations between BMI decrease and the NYD-SP18 and TMEM18 variants were found. Associations between all anthropometrical and biochemical changes and genes remained non-significant after data were adjusted for sex, age, and baseline values. CONCLUSIONS Decreased body weight in overweight/obese children is not significantly influenced by the NYD-SP18 rs6971091 or TMEM18 rs4854344 polymorphisms.
- MeSH
- adipozita genetika MeSH
- cvičení MeSH
- dítě MeSH
- genotyp MeSH
- hmotnostní úbytek genetika MeSH
- index tělesné hmotnosti MeSH
- jaderné proteiny genetika metabolismus MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- membránové proteiny genetika metabolismus MeSH
- mladiství MeSH
- nadváha genetika MeSH
- obezita genetika MeSH
- tělesná hmotnost genetika MeSH
- životní styl MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND & AIMS: We assessed orosensory detection of a long-chain fatty acid, linoleic acid (LA), and a bitter taste marker, 6-n-propylthiouracil (PROP), and correlated lipid-taster subjects with PROP detection and polymorphism in genes encoding bitter and lipid taste receptors, respectively, TAS2R38 and CD36, in normal weight and obese subjects. DESIGN: The normal weight (n = 52, age = 35.3 ± 4.10 years, BMI = 23.22 ± 1.44 kg/m2) and obese (n = 52, age = 35.0 ± 5.43 years, BMI = 34.29 ± 5.31 kg/m2) participants were recruited to determine fat and bitter detection thresholds. The genomic DNA was used to determine single nucleotide polymorphism (SNP) of CD36 (rs1761667) and TAS2R38 (rs1726866 and rs10246939). RESULTS: The study included the participants who could detect LA, i.e., lipid-tasters. There was a positive correlation between BMI and detection thresholds for fat and bitter taste in normal weight and obese subjects. Obese participants showed a positive correlation between LA and PROP detection thresholds. PROP detection thresholds were higher for CD36 SNP (rs1761667) and TAS2R38 SNPs (rs1726866 and rs10246939) in obese participants compared to normal weight subjects. LA detection thresholds were not high for CD36 SNP (rs1761667) or TAS2R38 SNP (rs1726866 and rs10246939) in obese participants. CONCLUSIONS: Orosensory detection thresholds for fat and bitter taste are associated with BMI, and CD36 and TAS2R38 genotypes are not always associated with taste phenotypes.
- MeSH
- antigeny CD36 genetika MeSH
- chuť genetika MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- obezita * epidemiologie genetika MeSH
- propylthiouracil MeSH
- receptory spřažené s G-proteiny genetika MeSH
- studie případů a kontrol MeSH
- tělesná hmotnost genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Using farmed common carp, we investigated the genetic background of the second year overwintering performance and its relation to the performance during the third growing season and at market size. The experimental stock was established by partial factorial design with a series of 4 factorial matings of 5 dams and 10 sires each. The families were reared communally and pedigree was re-constructed with 93.6% success using 12 microsatellites on 2008 offspring. Three successive recordings (second autumn, third spring, and third autumn-market size) covering two periods (second overwintering, third growing season) were included. Body weight, Fulton's condition factor and percent muscle fat content were recorded at all times and headless carcass yield and fillet yield were recorded at market size. Specific growth rate, absolute and relative fat change and overall survival were calculated for each period. Heritability estimates were significantly different from zero and almost all traits were moderately to highly heritable (h2 = 0.36-1.00), except survival in both periods and fat change (both patterns) during overwintering (h2 = 0.12-0.15). Genetic and phenotypic correlations imply that selection against weight loss and fat loss during overwintering is expected to lead to a better winter survival, together with a positive effect on growth in the third growing season. Interestingly, higher muscle fat content was genetically correlated to lower survival in the following period (rg = -0.59; -0.53, respectively for winter and the third summer). On the other hand, higher muscle fat was also genetically linked to better slaughter yields. Moreover, selection for higher condition factor would lead to better performance during winter, growing season and at market size.
- MeSH
- chov zvířat metody MeSH
- fenotyp MeSH
- kapři genetika růst a vývoj metabolismus MeSH
- kvantitativní znak dědičný MeSH
- maso analýza MeSH
- mikrosatelitní repetice genetika MeSH
- modely genetické MeSH
- složení těla genetika MeSH
- tělesná hmotnost genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.
- MeSH
- bazální metabolismus genetika MeSH
- celogenomová asociační studie MeSH
- diabetes mellitus 2. typu genetika MeSH
- fenotyp MeSH
- genové regulační sítě MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- metabolické nemoci genetika MeSH
- myši knockoutované MeSH
- myši MeSH
- obezita genetika MeSH
- plocha pod křivkou MeSH
- rychlé screeningové testy MeSH
- spotřeba kyslíku genetika MeSH
- tělesná hmotnost genetika MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- dyslipidemie komplikace metabolismus MeSH
- energetický metabolismus fyziologie imunologie MeSH
- financování organizované MeSH
- hnědá tuková tkáň metabolismus patologie MeSH
- inzulinová rezistence * genetika imunologie MeSH
- lidé MeSH
- metabolismus lipidů fyziologie genetika MeSH
- obezita komplikace metabolismus MeSH
- rizikové faktory * MeSH
- stárnutí * fyziologie metabolismus patologie MeSH
- statistika jako téma MeSH
- tělesná hmotnost fyziologie genetika imunologie MeSH
- triglyceridy izolace a purifikace metabolismus škodlivé účinky MeSH
- Check Tag
- lidé MeSH
Dementias of old age, in particular Alzheimer's disease (AD), pose a growing threat to the longevity and quality of life of individuals as well as whole societies world-wide. The risk factors are both genetic and environmental (life-style) and there is an overlap with similar factors predisposing to cardiovascular diseases (CVD). Using a case-control genetic approach, we have identified a SNP (rs10507391) in ALOX5 gene, previously associated with an increased risk of stroke, as a novel genetic risk factor for AD. ALOX5 gene encodes a 5'-lipoxygenase (5'-LO) activating protein (FLAP), a crucial component of the arachidonic acid/leukotriene inflammatory cascade. A-allele of rs4769874 polymorphism increases the risk of AD 1.41-fold (p<0.0001), while AA genotype does so 1.79-fold (p<0.0001). In addition, GG genotype of rs4769874 polymorphism is associated with a modest increase in body mass index (BMI). We discuss potential biochemical mechanisms linking the SNP to AD and suggest possible preventive pharmacotherapies some of which are based on commonly available natural products. Finally, we set the newly identified AD risk factors into a broader context of similar CVD risk factors to generate a more comprehensive picture of interacting genetics and life-style habits potentially leading to the deteriorating mental health in the old age.
- MeSH
- Alzheimerova nemoc genetika patofyziologie psychologie MeSH
- arachidonát-5-lipoxygenasa genetika MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- index tělesné hmotnosti * MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- průzkumy a dotazníky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tělesná hmotnost genetika MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING: The funding sources are cited at the end of the paper.
- MeSH
- diabetes mellitus 2. typu genetika MeSH
- genetické testování MeSH
- HDL-cholesterol metabolismus MeSH
- hydroxymethylglutaryl-CoA-reduktasy genetika MeSH
- index tělesné hmotnosti MeSH
- jednonukleotidový polymorfismus genetika MeSH
- LDL-cholesterol metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- rizikové faktory MeSH
- senioři MeSH
- statiny škodlivé účinky MeSH
- tělesná hmotnost genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
1. Changes in embryonic development and growth were analysed in relation to direct changes in postnatal growth and correlated responses in egg parameters using Japanese quail lines selected for more than 30 generations for high (HG) and low (LG) relative gain of body weight (BW) between 11 and 28 d of age, and constant BW at 49 d of age. 2. During the first 42 h as well as at the end of incubation, LG embryos were developmentally accelerated in comparison with their HG counterparts. An expected increase of line divergence across generations was observed only in traits analysed at the end of incubation. 3. In contrast to early generations, LG embryos continuously exhibited a higher BW than HG embryos and this difference temporarily disappeared only around incubation d 8. Analogous to early generations, the HG compared with LG embryos showed two periods of transient growth retardation compensated subsequently by a higher growth rate (incubation d 3-8 and 8-16). 4. More pronounced growth retardation of HG versus LG embryos in late versus early generations corresponded to more distinct decrease of HG versus LG growth rate during the first post-hatch days. Likewise, a disappearance of line BW differences on incubation d 8 characterising the late generations corresponded to the elimination of line differences in adult BW. 5. Alterations of growth pattern were associated with changes of egg size. While HG quail maintained a relatively constant adult BW and egg size across generations, the gradually increasing incidence of large eggs in the LG line allowed selection of birds with higher growth potential, which in turn amplified the line differences in the embryonic BW and eliminated the line differences in adult BW. Line differences in egg composition (larger albumen with lower density in LG compared with HG eggs) apparently contributed to the strengthening of line developmental divergence during incubation. 6. Transient lack of nutrient supply to HG embryos due to their developmental delay is probably responsible for a higher HG versus LG embryo mortality.
- MeSH
- časové faktory MeSH
- Coturnix embryologie genetika růst a vývoj MeSH
- embryonální vývoj genetika MeSH
- selekce (genetika) * MeSH
- tělesná hmotnost genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Obezita a její komorbidity představují v současné době jeden z největších zdravotních problémů. V celosvětovém nárůstu prevalence obezity v posledních několika desetiletích hraje klíčovou roli pozitivní energetická bilance v důsledku nežádoucích změn životního stylu. Vliv genetických faktorů je rovněž podstatný – několik studií dospělo k závěru, že geny přispívají k rozvoji obezity ze 40–70 %. Genetická variabilita předurčuje jedince k náchylnosti či rezistenci navyšovat tělesnou hmotnost v interakci s obezitogenním prostředím. Ačkoliv se u naprosté většiny obézních jedinců jedná o tzv. polygenní typ dědičnosti, výzkum za posledních 20 let identifikoval nositele mutací genů způsobujících tzv. monogenně podmíněnou obezitu. Dosud bylo identifikováno jen několik genů (pro leptin, leptinový receptor, prohormon konvertázu 1, proopiomelanokortin, melanokortinový receptor 4. typu, single-minded homolog 1, brain-derived neurotrophic factor a receptor neurotrofické tyrozinové kinázy 2. typu), které se buď podílejí na neuronální diferenciaci hypothalamu, nebo jsou součástí leptino-melanokortinové signalizační osy. Nositelé mutací se kromě časně vzniklé obezity s hyperfagií dále vyznačují např. adrenální insuficiencí, poruchou imunity a fertility. Předkládaný přehledový článek rekapituluje aktuální stav molekulárně-genetického a klinického výzkumu v oblasti monogenně podmíněné obezity včetně terapeutických možností.
Obesity and its comorbidities represent one of the major health problems worldwide. A positive energy balance due to inappropriate life-style changes plays a key role in the current obesity epidemic. The influence of genetic factors is also significant – several studies concluded that genes contribute to the development of obesity by 40–70%. Genetic variability predisposes an individual to tendency or resistance to increase body weight in obesogenic environment. Polygenic type of inheritance is responsible in most of obese individuals. However, an intensive research of the past 20 years has led to an identification of several genes causing monogenic forms of obesity. To date, several monogenic genes (leptin, leptin receptor, prohormon convertase 1, proopiomelanocortin, melanocortin 4 receptor, single-minded homolog 1, brain-derived neurotrophic factor, neurotrophic tyrosine kinase receptor type 2) that are either involved in the neuronal differentiation of the paraventricular nucleus or in the leptin-melanocortin pathway are known to cause obesity. Mutation carriers apart from severe early onset obesity manifest with additional phenotypic characteristics as adrenal insufficiency, impaired immunity and impaired fertility. This review provides an overview of molecular-genetic and clinical research in the field of monogenic obesities including therapeutical approaches.
- MeSH
- centrální nervový systém MeSH
- dítě MeSH
- dospělí MeSH
- energetický metabolismus MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- genetické nemoci vrozené MeSH
- leptin fyziologie MeSH
- leptinové receptory genetika účinky léků MeSH
- lidé MeSH
- molekulární biologie MeSH
- mozkový neurotrofický faktor genetika MeSH
- mutace genetika MeSH
- obezita * genetika MeSH
- polymorfismus genetický MeSH
- pro-opiomelanokortin genetika MeSH
- proproteinkonvertasa 1 genetika MeSH
- receptor melanokortinový typ 3 genetika MeSH
- receptor melanokortinový typ 4 genetika MeSH
- tělesná hmotnost genetika MeSH
- transkripční faktory genetika MeSH
- výzkum MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
