Higher Energy Intake Variability as Predisposition to Obesity: Novel Approach Using Interquartile Range.

OBJECTIVE: It is known that total energy intake and its distribution during the day influences human anthropometric characteristics. However, possible association between variability in total energy intake and obesity has thus far remained unexamined. This study was designed to establish the influence of energy intake variability of each daily meal on the anthropometric characteristics of obesity. METHODS: A total of 521 individuals of Czech Caucasian origin aged 16­73 years (390 women and 131 men) were included in the study, 7-day food records were completed by all study subjects and selected anthropometric characteristics were measured. The interquartile range (IQR) of energy intake was assessed individually for each meal of the day (as a marker of energy intake variability) and subsequently correlated with body mass index (BMI), body fat percentage (%BF), waist-hip ratio (WHR), and waist circumference (cW). RESULTS: Four distinct models were created using multiple logistic regression analysis and backward stepwise logistic regression. The most precise results, based on the area under the curve (AUC), were observed in case of the %BF model (AUC=0.895) and cW model (AUC=0.839). According to the %BF model, age (p<0.001) and IQR-lunch (p<0.05) seem to play an important prediction role for obesity. Likewise, according to the cW model, age (p<0.001), IQR-breakfast (p<0.05) and IQR-dinner (p <0.05) predispose patients to the development of obesity. The results of our study show that higher variability in the energy intake of key daily meals may increase the likelihood of obesity development. CONCLUSIONS: Based on the obtained results, it is necessary to emphasize the regularity in meals intake for maintaining proper body composition.

Per3 VNTR polymorphism and chronic heart failure.

AIMS: The aim of this study was to investigate the relationship between gene Period3 (Per3) variable number tandem repeat (VNTR) polymorphism and chronic heart failure (CHF). METHODS: The study subjects (372 patients of Caucasian origin with CHF and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific PCR. RESULTS: No significant differences in genotype or Per3 VNTR allele frequencies were found between CHF cases and controls (Pg=0.30, Pa=0.52). No significant differences were uncovered either between CHF cases according to etiology (DCMP vs. IHD; Pg=0.87, Pa=0.91). In the multivariate regression modeling, no predictive function of VNTR Per3 polymorphism on ejection fraction or NYHA class, hyperlipidaemia or type II diabetes risk was found. CONCLUSION: Per3 VNTR polymorphism is not a major risk factor for chronic heart failure or a factor modulating the severity of the CHF in this population.

Variability in CNR1 locus influences protein intake and smoking status in the Central-European population.

OBJECTIVES: The endocannabinoid receptor 1 (CB1) is encoded by the CNR1 gene and has been recently recognized to play an important role in the regulation of satiety and feeding behaviour with a huge potential of modulating metabolic response and feeding control. The aim of the study was to investigate the potential of three selected single nucleotide polymorphisms (SNPs) in the CNR1 locus on native dietary composition in the Central-European Caucasian population. METHODS: A total of 258 unrelated individuals originating from the Central-European Caucasian population were enrolled into the study and rs1049353, rs12720071, and rs806368 polymorphisms in CNR1 locus were examined in these individuals using PCR-based methodology. Body composition was assessed using a bioimpedance method, various anthropometric parameters were investigated (waist and hip circumference, skin folds), and native dietary composition was analysed using 7-day food records as well as a food frequency questionnaire. RESULTS: Allelic variations and common haplotypes in the CNR1 gene were associated with the daily intake of proteins, fluids, and fibre, regardless of the physical activity of the individuals. The common haplotype in the CNR1 gene was associated with self-reported smoking (number of cigarettes per day, smoking years). DISCUSSION: Our results indicate that specific genetic variations in the CNR1 gene may act as susceptibility markers for specific dietary composition in the Central-European population.

A common variation in the cannabinoid 1 receptor (CNR1) gene is associated with pre-eclampsia in the Central European population.

OBJECTIVE: Recently it has been proposed that tightly regulated levels of endogenous cannabinoids play a fundamental role in early placental development. The aim of this study was to investigate associations of three single-nucleotide polymorphisms (SNPs) in the cannabinoid 1 receptor (CNR1) gene (rs1049353, rs12720071 and rs806368) and their inferred haplotypes with pre-eclampsia, a severe pregnancy-associated condition characterized by abnormal development and remodeling of spiral decidual arteries. STUDY DESIGN: The case-control study comprised a total of 115 pre-eclamptic women and 145 healthy pregnant controls, all originating from the Central-European Czech population. Using PCR-based methods, we tested rs1049353, rs12720071 and rs806368 in the CNR1 gene and haplotypes were constructed. RESULTS: Statistically significant difference in genotype distributions of rs806368 (p(g)<10(-3)) was observed when comparing the cases and the controls; the cases presenting with significantly lower proportion of CC homozygotes. In multivariate modeling, the rs806368 served as a predictor for pre-eclampsia development (ß=0.15; p=0.04). Haplotype analysis revealed presence of four common haplotypes; the CAA haplotype being less frequent in pre-eclamptic cases compared to the controls (p<0.008). Analysis of regression models confirmed the independent prediction role of AAC haplotype for pre-eclampsia onset (ß=-0.18; p=0.03). CONCLUSION: This is the first study focusing on the relationship between SNPs in the CNR1 gene and pre-eclampsia risk. Although limited by a relatively small sample size, the study indicates that rs806368 in the CNR1 gene may act as a susceptibility marker for pre-eclampsia in humans.

Circulating Levels of Agouti-Related Peptide in Endometrial Cancer Survivors.

BACKGROUND: Recently, it has been reported that central administration of agouti-related peptide (AgRP) might have protective effect against cachexia development in tumor-bearing mice. In this study, we determined whether the disease-free endometrial cancer survivors present with different plasma AgRP levels than controls and whether there was an association with the duration of the disease-free interval. METHODS: The total of 53 endometrial cancer survivors was enrolled in the study along with 93 healthy control women of similar age. Fasting blood samples were obtained and AgRP plasma levels determined using ELISA-based methodology. RESULTS: The AgRP plasma levels were significantly higher in the cases than in the controls; AgRP levels were the lowest in obese control women (77.4 ± 19.8 pg/ml); on the contrary, the AgRP plasma levels were highest in non-obese cancer survivors (100.5 ± 21.12 pg/ml). Moreover, we observed significant differences in AgRP levels between the endometrial cancer survivors and the control subjects [p (for comparison of the cases and the controls) = 0.002]. In the regression modeling, AgRP was significantly associated with the BMI as well as the case-control status, and the case-control differences in AgRP levels retained their statistical significance also after adjustment for BMI. CONCLUSIONS: Disease-free endometrial cancer survivors who did not develop cachexia during their treatment as well as post-treatment period present with significantly higher AgRP levels than the control population, independently on their BMI and menopausal status which could be indicative of the protective effect of circulating AgRP against cachexia development in endometrial cancer.

Comparison of agouti-related peptide levels in peripheral blood of postpartum pre-eclamptic and non pre-eclamptic women and in umbilical cord blood from their pregnancies.

Plasma levels of agouti-related peptide (AgRP) were reported to continuously rise during ongoing pregnancy in rats. The aim of the study was to investigate the maternal pre-partum peripheral plasma levels of AgRP and levels in umbilical cord blood in pre-eclamptic and physiological pregnancies in humans.

Common polymorphism +45T/G in adiponectin gene as potential modulator of in-stent restenosis development.

Adiponectin has been reported previously to be associated with in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). This paper discusses possible associations between ISR after PCI and the +45T/G polymorphism in the adiponectin locus.

Genotype x nutrient association of common polymorphisms in obesity-related genes with food preferences and time structure of energy intake.

Personal food preferences can either enhance or suppress the development of obesity and the selection and proportion of macronutrients in the diet seem to have a heritable component. In the present study, we therefore focused on dietary composition as a specific trait related to obesity and we determined whether genetic variations in leptin (LEP), LEP receptor (LEPR), adiponectin (ADIPOQ), IL-6 and pro-opiomelanocortin (POMC) underlie specific native food preferences and obesity-related anthropometric parameters. The total of 409 individuals of Czech Caucasian origin were enrolled into the present study and 7 d food records were obtained from the study subjects along with selected anthropometric measurements. In a subset of study subjects, plasma levels of ADIPOQ, LEP and soluble LEPR were measured. Independently of the BMI of the individuals, common variations in LEP and LEPR genes were associated with specific eating patterns, mainly with respect to timing of eating. The LEP + 19A/G polymorphism served as an independent predictor for BMI, percentage of body fat and skinfold thickness and significantly affected the time structure of the daily energy intake. The POMC RsaI polymorphism was associated with percentage of body fat. The ADIPOQ 45 T/G polymorphism was associated with the thickness of the subscapular skinfold. The LEPR Gln223Arg polymorphism was associated with multiple parameters, including diastolic blood pressure, meal sizes during the day and plasma ADIPOQ levels. In a separate analysis, soluble leptin receptor (sObR) plasma levels and LEP:sObR ratio were significantly correlated with systolic blood pressure (beta = - 0.66, P = 0.002; beta = - 1.23, P = 0.02) and sObR plasma levels also served as an independent predictor for diastolic blood pressure (beta = - 0.50; P = 0.04). To conclude, we report common allelic variants associated with specific feeding behaviour and obesity-related anthropometric traits. Moreover, we identified allelic variants that significantly influence the time structure of food intake during the day.

Effect of ID ACE gene polymorphism on dietary composition and obesity-related anthropometric parameters in the Czech adult population.

The aim of this study was to investigate the possible associations between insertion/deletion (ID) polymorphism in angiotensin-converting enzyme (ACE) (dbSNP rs 4646994) with the food intake and body composition in the Czech non-obese, obese and extremely obese populations. A total of 453 various-weighted individuals were enrolled in the study and were according to their BMI assigned into following subgroups, such as obese (30 /=40) and non-obese (20 < BMI < 30) subjects. Both the obese cases and the non-obese controls underwent the identical subset of standardized examinations (BMI, % body fat, waist-to-hip ratio, skin fold thickness, native dietary composition examined by 7-day food records, etc.). No significant case-control differences in genotype distributions or allelic frequencies were observed. There were no differences in genotype frequencies between males and females either. The prevalence of obesity was significantly higher among subjects with the II genotype (42 %) when compared with those with DD (36%) and those with ID (37%) genotypes (P = 0.04). When compared with carbohydrate intake in the whole studied cohort, the odds ratios of carrying the DD allele in the morbidly obese cohort were 0.84 (95% CI 0.34, 2.10, P = 0.17), 0.27 (0.07, 0.98, P = 0.02), and 4.25 (1.44, 12.51, P = 0.005) in those individuals consuming <210, 210-260, and >260 g of carbohydrates/day, respectively. Based on our findings, the ID ACE polymorphism could represent a gene modulator of carbohydrate intake in morbidly obese Czech population; the strong significant effect of DD genotype was observed in the phenotypes of extreme obesity with the highest carbohydrate intake.

Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population.

Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II-IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56-2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36-10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69-3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20-3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08-55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential CHF susceptibility genes is unclear. Based on our findings, the LEPR Gln223Arg polymorphism could be considered a disease susceptibility modulating factor both in ischemic heart disease or dilated cardiomyopathy patients.

Relation between adiponectin 45 T/G polymorphism and dietary composition in the Czech population.

In this study on 138 Czech Caucasians, the ADIPOQ 45T/G polymorphism was associated with the dietary composition. As the GG homozygotes were associated with the increased intake of carbohydrates, we suggest that a proportion of the prodiabetogenic effect of the polymorphism might be due to its influence on eating behaviour.

Is there any link between severe pre-eclampsia and defined polymorphisms in leptin and adiponectin genes?

AIM: The pathophysiology of pre-eclampsia, one of the leading causes of maternal mortality worldwide, still remains unclear. Recently, it has been suggested that impaired regulation of complex interactions among various adipokines plays an important role in the development of pre-eclampsia. The aim of this study was to investigate whether the two common polymorphisms of the leptin (LEP) and adiponectin (APM1) genes are associated with the development of pre-eclampsia and its related traits (gestational hypertension, proteinuria and various measures of reduced fetal growth ) in the Czech pre-eclamptic population. METHODS: The case-control study comprised a total of 123 pre-eclamptic women and 150 healthy controls of similar age and parity distribution. They were genotyped for the LEP -2548G/A (5'-untranslated region) and APM1 T94G (exon 2) polymorphisms using polymerase chain reaction. RESULTS: The allele frequency of the LEP -2548G polymorphism was 0.541 in the pre-eclamptic group versus 0.583 in the control group (P=0.578); the frequency of the APM1 94G polymorphism was 0.073 and 0.079 (P=0.628), respectively. No significant associations were detected between either of the two single nucleotide polymorphisms or any of the parameter biomarkers related to pre-eclampsia, such as gestational hypertension or proteinuria. However, the APM1 T94G polymorphism was significantly associated with a low birth weight in pre-eclamptic pregnancies, with mothers carrying the T-allele having an almost three-fold increase in the likelihood of giving birth to a child with a low birth weight for its gestational age (odds ratio, 2.7; 95% confidence interval, 0.18-5.9; P=0.004). CONCLUSIONS: The APM1 T94G and LEP -2548G/A polymorphisms do not seem to be major genetic determinants of susceptibility to pre-eclampsia in the Czech Caucasian population. However, evidence has been provided for possible APM1 T94G involvement in controlling the birth weight of children from pre-eclamptic pregnancies, thus supporting the hypothesis of T94G involvement in controlling the birth weight of newborns.

No association of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin gene with food preferences in the Czech population.

BACKGROUND: Previously, it has been reported that mutations in the genes encoding for adipokines may be associated with impaired food intake and may serve as potential obesity biomarkers. The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes. PATIENTS AND METHODS: Using PCR followed by restriction analysis, we studied 185 volunteers. Basic anthropometrical characteristics associated to obesity were measured and the food intake was monitored using a 7-day record method. In the group of obese individuals, a subset of 34 morbidly obese patients was studied for plasma leptin and soluble leptin receptor levels. RESULTS: None of the examined polymorphisms was associated to anthropometrical or demographic characteristics of the study subjects. The Gln223Arg polymorphism within the leptin receptor gene was significantly associated with lower plasma leptin levels (the RR genotype being more frequent in patients with lower plasma leptin levels; P = 0.001). No associations of the examined polymorphisms with food preferences was observed. CONCLUSIONS: Based on our results, the examined polymorphisms in the adipokine genes do not seem to be the major risk factor for obesity development in the Czech population nor significantly affect food preferences.

Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus.

The aim of this study was to investigate possible associations of -2548 G/A polymorphism in leptin gene promoter and pregnancy-associated diseases with abnormal fetal growth such as preeclampsia and gestational diabetes. The study was also focused on whether it is rather maternal or fetal variants that determines the pathological growth status. Peripheral or cord blood samples obtained from 49 preeclamptic women and their 39 newborns, 53 healthy controls and their 53 healthy newborns and 48 patients with gestational diabetes mellitus were evaluated for leptin gene (LEP) locus -2548 genotypes. The significantly higher risk for gestational diabetes mellitus was observed in the presence of an allele (AA and AG genotypes) against carriers of GGgenotype(OR=2.84, 95%CI1.14-7.07,p=0.02). Thereisa significant risk of diabetes mellitus associated to A allele (OR=1.79, 95%CI 1.02-3.14, p=0.03). Furthermore, evaluations of preeclamptic patients' data revealed a significant association of genotype distribution and delivery and spontaneous abortion rate, where the GG carriers performed the highest pregnancy rate while the AG carriers performed the lowest spontaneous abortion rate. Our results support the hypothesis for -2548 G/A leptin gene polymorphism involvement in ethiopathogenesis of pregnancy-associated diseases with abnormal fetal growth, especially gestational diabetes mellitus.