Genetic predisposition to adiposity is associated with increased objectively assessed sedentary time in young children.

Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.

Maternal and fetal genetic contribution to gestational weight gain.

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Eating behaviour is associated with eating frequency and food consumption in 6-8 year-old children: The Physical Activity and Nutrition in Children (PANIC) study.

The association between eating behaviour and dietary factors has been studied narrowly in children. Therefore, we investigated whether eating frequency and food consumption are influenced by eating behaviour in a population sample of 406 children aged 6-8 years. We assessed features of eating behaviour by the Children's Eating Behaviour Questionnaire and dietary factors by a 4-day food record. The results showed that enjoyment of food was directly associated with a number of main meals (p = 0.041) and consumption of vegetables (p = 0.041), cheese (p = 0.005), and meat (p = 0.002). Food responsiveness was directly associated with consumption of fruit and berries (p = 0.013) and meat (p = 0.016). Desire to drink was directly associated with consumption of fat-containing milk (p = 0.002) and inversely associated with consumption of skimmed milk (p = 0.001). Food fussiness was inversely associated with a number of main meals (p = 0.013) and consumption of vegetables (p < 0.001), cheese (p = 0.001), and meat (p = 0.027). Satiety responsiveness was inversely associated with consumption of vegetables (p = 0.031), cheese (p = 0.010), and meat (p < 0.001) and directly associated with consumption of candies and chocolate (p = 0.026). Slowness in eating was inversely associated with consumption of meat (p = 0.018). Where sex differences existed the associations tended to be observed mostly in girls but not in boys. Our study shows that enjoyment of food and food responsiveness are directly associated with consumption of protein-rich foods and vegetables, fruit and berries, whereas food fussiness and satiety responsiveness are inversely associated with consumption of these foods. Assessment of eating behaviour can help in identifying children with various dietary needs.

Dietary quality indices in relation to cardiometabolic risk among Finnish children aged 6-8 years - The PANIC study.

BACKGROUND AND AIMS: There are no studies on the relationships of dietary quality indices to the clustering of cardiometabolic risk factors in children. We therefore investigated the associations of four dietary quality indices with cardiometabolic risk score and cardiometabolic risk factors in Finnish children. METHODS AND RESULTS: Subjects were a population sample of 204 boys and 198 girls aged 6-8 years. We assessed diet by 4-day food records and calculated Dietary Approaches to Stop Hypertension (DASH) Score, Baltic Sea Diet Score (BSDS), Mediterranean Diet Score (MDS), and Finnish Children Healthy Eating Index (FCHEI). We calculated the age- and sex-adjusted cardiometabolic risk score summing up Z-scores for waist circumference, mean of systolic and diastolic blood pressure and concentrations of fasting serum insulin and fasting plasma glucose, triglycerides and HDL cholesterol, the last multiplying by -1. Higher FCHEI was associated with lower cardiometabolic risk score among boys (standardised regression coefficient ß = -0.14, P = 0.044) adjusted for age, physical activity, electronic media time and household income. Higher DASH Score was related to a lower serum insulin in boys (ß = -0.15, P = 0.028). Higher DASH Score (ß = -0.16, P = 0.023) and FCHEI (ß = -0.17, P = 0.014) were related to lower triglyceride concentration in boys. Higher FCHEI was associated with lower triglyceride concentration in girls (ß = -0.16, P = 0.033). Higher DASH Score (ß = -0.19, P = 0.011) and BSDS (ß = -0.23, P = 0.001) were associated with lower plasma HDL cholesterol concentration in girls. CONCLUSION: Higher FCHEI was associated with lower cardiometabolic risk among boys, whereas DASH Score, BSDS or MDS were not associated with cardiometabolic risk in children.

Associations of cardiorespiratory fitness, physical activity, and adiposity with arterial stiffness in children.

Associations of cardiorespiratory fitness (CRF), physical activity (PA), sedentary behavior, and body fat percentage (BF%) with arterial stiffness and dilation capacity were investigated in 160 prepubertal children (83 girls) 6-8 years of age. We assessed CRF (watts/lean mass) by maximal cycle ergometer exercise test, total PA, structured exercise, unstructured PA, commuting to and from school, recess PA and total and screen-based sedentary behavior by questionnaire, BF% using dual-energy X-ray absorptiometry, and arterial stiffness and dilation capacity using pulse contour analysis. Data were adjusted for sex and age. Poorer CRF (standardized regression coefficient ß = -0.297, P < 0.001), lower unstructured PA (ß = -0.162, P = 0.042), and higher BF% (ß = 0.176, P = 0.044) were related to higher arterial stiffness. When CRF, unstructured PA, and BF% were in the same model, only CRF was associated with arterial stiffness (ß = -0.246, P = 0.006). Poorer CRF was also related to lower arterial dilation capacity (ß = 0.316, P < 0.001). Children with low CRF (< median) and high BF% (≥ median; P = 0.002), low CRF and low unstructured PA (< median; P = 0.006) or children with low unstructured PA and high BF% (P = 0.005) had higher arterial stiffness than children in the opposite halves of these variables. Poor CRF was independently associated with increased arterial stiffness and impaired arterial dilation capacity among children.

Plasma polyunsaturated fatty acids are directly associated with cognition in overweight children but not in normal weight children.

AIM: Polyunsaturated fatty acids are essential nutrients for the normal development of the brain. We investigated the associations between plasma polyunsaturated fatty acids and cognition in normal weight and overweight children. METHODS: The study recruited 386 normal weight children and 58 overweight children aged six to eight years and blood samples were drawn after a 12-hour fast. We assessed plasma polyunsaturated fatty acids using gas chromatography, cognition using Raven's Coloured Progressive Matrices, and overweight and obesity using the age-specific and sex-specific cut-offs from the International Obesity Task Force. The data were analysed by linear regression analyses adjusted for age and sex. RESULTS: Higher proportions of eicosapentaenoic acid in plasma triacylglycerols (ß = 0.311, p = 0.020, p = 0.029 for interaction) and docosahexaenoic acid in plasma triacylglycerols (ß = 0.281, p = 0.038, p = 0.049 for interaction) were both associated with higher Raven's scores in overweight children but not in normal weight children. Higher eicosapentaenoic acid to arachidonic acid ratios in triacylglycerols (ß = 0.317, p = 0.019) and phospholipids (ß = 0.273, p = 0.046) were directly associated with the Raven's score in overweight children but not in normal weight children. CONCLUSION: These findings suggest that increasing the consumption of fish and other sources of eicosapentaenoic acid and docosahexaenoic acid may improve cognition among overweight children.

Dietary factors associated with metabolic risk score in Finnish children aged 6-8 years: the PANIC study.

PURPOSE: Previous evidence for the associations of eating frequency and food consumption with clustering of metabolic risk factors among children is limited. We therefore investigated association of the daily number of main meals and snacks and food consumption with a metabolic risk score and individual metabolic risk factors in primary school children. METHODS: The subjects were a population sample of Finnish girls and boys 6-8 years of age. Dietary factors were measured by a four-day food record. Metabolic risk score was calculated summing up the Z-scores of waist circumference, systolic and diastolic blood pressure, and concentrations of fasting serum insulin and fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol, the latest multiplying by -1. RESULTS: Skipping main meals (standardized regression coefficient ß = -0.18, P < 0.001), a higher consumption of non-root vegetables (ß = 0.18, P < 0.01), low-fat vegetable-oil-based margarine (ß = 0.13, P < 0.01) and sugar-sweetened beverages (ß = 0.11, P < 0.05) and a lower consumption of vegetable oils (ß = -0.10, P < 0.05) were associated with a higher metabolic risk score after adjustment for age, sex, total physical activity, electronic media time, energy intake and other dietary factors. The consumption of red meat was directly related to the metabolic risk score, but the association was not statistically significant after adjustment for energy intake. CONCLUSIONS: Eating main meals regularly, decreasing the consumption of sugar-sweetened beverages and low-fat margarine and increasing the consumption of vegetable oils should be emphasized to reduce metabolic risk among children.

Dietary factors associated with overweight and body adiposity in Finnish children aged 6-8 years: the PANIC Study.

OBJECTIVES: To investigate the associations of dietary factors with overweight, body fat percentage (BF%), waist circumference (WC) and hip circumference (HC) among children. DESIGN: Cross-sectional analysis of the Physical Activity and Nutrition in Children (PANIC) Study among 510 children (263 boys, 247 girls) aged 6-8 years from Kuopio, Finland. METHODS: The children's weight, height, WC and HC were measured. Overweight was defined by International Obesity Task Force body mass index cutoffs. The BF% was measured by dual-energy X-ray absorptiometry, nutrient intakes and meal frequency by 4-day food records and eating behaviour by Children's Eating Behaviour Questionnaire. RESULTS: Daily consumption of all the three main meals was inversely associated with overweight (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.18-0.75), BF% (ß -0.12, P = 0.012), WC (ß -0.16, P = 0.002) and HC (ß -0.15, P = 0.002). Enjoyment of food, food responsiveness and emotional overeating were directly associated with overweight (OR 1.57, 95% CI 1.04-2.35; OR 4.68, 95% CI 2.90-7.54; OR 2.60, 95% CI 1.52-4.45, respectively), BF% (ß 0.13, P = 0.004; ß 0.30, P<0.001; ß 0.09, P = 0.035, respectively), WC (ß 0.14, P = 0.003; ß 0.40, P<0.001; ß 0.19, P<0.001, respectively) and HC (ß 0.15, P = 0.001; ß 0.38, P<0.001; ß 0.15, P = 0.001, respectively). Satiety responsiveness was inversely associated with overweight (OR 0.42, 95% CI 0.26-0.67), BF% (ß -0.20, P<0.001), WC (ß -0.26, P<0.001) and HC (ß -0.26, P<0.001). Slowness in eating was inversely associated with overweight (OR 0.61, 95% CI 0.41-0.92), WC (ß -0.16, P = 0.001) and HC (ß -0.17, P<0.001). Protein intake was directly associated with BF% (ß 0.11, P = 0.017), WC (ß 0.11, P = 0.020) and HC (ß 0.13, P = 0.008). CONCLUSIONS: Promoting regular consumption of main meals and healthy eating behaviours should be emphasized in the prevention of overweight among children. More research is needed on the association of protein-rich foods with body adiposity in children.

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study.

OBJECTIVE: Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. DESIGN: Randomized controlled and individualized weight reduction intervention. SUBJECTS: Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60+/-7 years were randomized either to a weight reduction (WR) (n=28) or a control (n=18) group lasting for 33 weeks. MEASUREMENTS: Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction > or =5%, n=9) and control group (n=10). The results were confirmed using quantitative PCR. RESULTS: In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S (I) and the change in body weight was found (r=-0.44, P=0.026). Downregulation of gene expression (P<0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (-39+/-16%, P<0.0001). Moreover, its expression correlated with insulin sensitivity (r=-0.34, P=0.005) before the intervention and with body adiposity both before (r=0.42, P=0.007) and after (r=0.30, P=0.056) the intervention. CONCLUSION: Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.

Associations of I148M variant in PNPLA3 gene with plasma ALT levels during 2-year follow-up in normal weight and overweight children: the PANIC Study.

OBJECTIVES: PNPLA3 I148M polymorphism (rs738409) has been strongly associated with liver fat content and plasma alanine aminotransferase (ALT) levels in obese adults and children, but little is known about these relationships in normal weight individuals. We studied the associations and interactions of overweight and the PNPLA3 I148M polymorphism with plasma ALT levels during 2-year follow-up in children. METHODS: Subjects were a population sample of 481 Caucasian children aged 6-8 years examined at baseline and 419 children re-examined after 2-year follow-up. Altogether, 58 (12%) of 481 children at baseline and 71 (17%) of 419 children after 2-year follow-up were overweight. We assessed plasma ALT levels and other cardiometabolic risk factors and genotyped the PNPLA3 I148M polymorphism. RESULTS: Being overweight and carrying PNPLA3 148M allele were associated with increased ALT levels at baseline (P = 0.002; P = 0.033) and after 2-year follow-up (P < 0.001; P = 0.001). Being overweight (P < 0.001) and carrying PNPLA3 148M allele (P = 0.001) were also associated with increase in ALT levels during 2-year follow-up. PNPLA3 148M allele carriers had increased ALT levels at baseline (P = 0.024 for interaction) and after 2-year follow-up (P = 0.002 for interaction) as well as a larger increase in ALT levels during 2-year follow-up (P = 0.002 for interaction) if they were overweight but not if they were normal weight. Further adjustment for clinical puberty, dietary factors, physical activity or sedentary behaviour had little or no effect on these associations. CONCLUSION: PNPLA3 148M allele carriers had higher plasma ALT levels and larger increase in ALT levels during follow-up than non-carriers only among overweight children.

APOE polymorphism and the hypertriglyceridemic effect of dietary sucrose.

BACKGROUND: The E4 allele of the apolipoprotein gene (APOE) is associated with a greater serum cholesterol response to dietary changes in fat and cholesterol. However, less is known about the interaction between APOE polymorphism and other macronutrients in the diet. OBJECTIVE: We evaluated the interaction between APOE polymorphism and dietary fat and carbohydrate, particularly sucrose, in relation to serum lipid concentrations. DESIGN: A total of 284 men and 130 women with coronary artery disease (mean age: 61 y; range: 33-74 y) participated in the cross-sectional EUROASPIRE study. Serum lipids and fatty acids in cholesteryl esters (CEs) were measured and APOE genotypes were determined. Dietary intake was examined by using a 4-d food record. RESULTS: Patients were grouped by APOE genotype: E2 (E2/E2 and E2/E3; n = 21), E3 (E3/E3; n = 245), and E4 (E4/E2, E4/E3, and E4/E4; n = 148). Patients with the E2 allele had lower LDL-cholesterol concentrations and tended to have higher triacylglycerol concentrations than did patients with the E3 or E4 allele; concentrations were not significantly different between the last 2 groups. In regression analysis, significant predictors of serum triacylglycerol were the interaction between sucrose intake and the E2 allele, proportion of n-3 fatty acids in CEs, body mass index, and diabetes. A high sucrose intake was associated with high triacylglycerol concentrations only in patients with the E2 allele. Interaction between saturated fat intake and the E2 allele, proportion of linoleic acid in CEs, and fiber intake predicted serum cholesterol. CONCLUSION: Coronary artery disease patients with the E2 allele will likely have a greater triacylglycerol response to high dietary sucrose intakes than will patients with the E3 or E4 allele.

Association of the PRO12ALA polymorphism of the PPAR-gamma2 gene with oxidized low-density lipoprotein and cardiolipin autoantibodies in nondiabetic and type 2 diabetic subjects.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a key component in adipocyte differentiation and fat-specific gene expression and may modulate macrophage functions, like proinflammatory activities, and stimulate oxidized low-density lipoprotein (ox-LDL) uptake. We hypothesized that the Pro12Ala polymorphism of the PPAR-gamma2 gene may affect the immune response to ox-LDL. Therefore, we investigated the association of the Pro12Ala polymorphism of the PPAR-gamma2 gene with ox-LDL autoantibodies, as well anticardiolipin antibodies, in a 10-year prospective study. The Pro12Ala polymorphism was genotyped in 119 nondiabetic subjects (age, 45 to 64 years; body mass index [BMI], 19 to 46 kg/m(2)) and 70 type 2 diabetic patients (age, 45 to 65 years; BMI, 19 to 46 kg/m(2)) by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method. Ox-LDL autoantibodies and anticardiolipin antibodies were determined at baseline and after 10 years of follow-up. At baseline, the Pro12Ala polymorphism was not associated with ox-LDL autoantibodies in nondiabetic subjects, whereas type 2 diabetic patients having the Pro12Ala or the Ala12Ala genotypes tended to have higher levels of ox-LDL autoantibodies than did type 2 diabetic patients with the Pro12Pro genotype. At the 10-year follow-up, diabetic subjects having the Ala12 allele had higher ox-LDL autoantibody levels than did diabetic subjects with the Pro12Pro genotype (P =.043 after adjustment for age, gender, BMI, and hemoglobin A(1c) [HbA(1c)] at 5 years). In nondiabetic subjects and regarding anticardiolipin antibodies, no such relationship was observed. We conclude that the Pro12Ala polymorphism of the PPAR-gamma2 gene was associated with increased ox-LDL autoantibodies in type 2 diabetic subjects. Genotype may therefore modulate the oxidative modification of LDL in hyperglycemic milieu.

Dietary factors and their associations with socioeconomic background in Finnish girls and boys 6-8 years of age: the PANIC Study.

BACKGROUND/OBJECTIVES: To study nutrient intake, food consumption and meal pattern, and their associations with socioeconomic background in Finnish children. SUBJECTS/METHODS: The subjects were a population sample of 424 children (211 girls, 213 boys) 6-8 years of age. Nutrient intake and meal pattern were measured by food records, and food intake and socioeconomic characteristics were assessed by questionnaires. RESULTS: Intakes of saturated fat, sucrose and salt were higher, and intakes of vitamin D, iron and fibre and unsaturated-to-saturated fat ratio lower than recommended. Less than 5% of children consumed vegetables, fruit and berries as recommended. Children with highest parental education more likely ate fish (odds ratio (OR) 2.20, 95% confidence interval (CI) 1.06-4.54), fibre-rich bread (OR 5.06, 95% CI 1.80-14.29) and main meals (OR 2.54, 95% CI 1.34-4.83), but less likely used soft margarine (OR 0.43, 95% CI 0.20-0.94) as recommended than children with lowest parental education. Children with highest household income more likely consumed skimmed milk (OR 2.43, 95% CI 1.21-4.88) and fish (OR 2.21, 95% CI 1.12-4.36) as recommended than children with lowest household income. Only 34% of girls and 45% of boys ate all main meals daily. Snacks provided as much as 42% of total energy intake. CONCLUSIONS: Children do not meet recommendations in all important nutrients. Children from lowest socioeconomic position least likely consumed fish, skimmed milk and fibre-rich bread and ate main meals, but most likely used soft margarine as recommended. Less than half of children ate all main meals daily.

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

AIMS: Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). METHODS: DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. RESULTS: There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). CONCLUSIONS: Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.

The effects of the Pro12Ala polymorphism of the PPARgamma-2 gene on lipid metabolism interact with body size at birth.

Body size at birth is an indicator of the intrauterine environment. The effects of the Pro12Pro genotype and the 12Ala allele of the PPARgamma-2 gene on glucose and insulin metabolism in adult life depend on body size at birth. A low birth weight is associated with insulin resistance and type 2 diabetes. The peroxisome proliferator-activated receptor-gamma (PPARgammas) are also regulators of adipocyte differentiation, and the PPARgamma-2 gene could also contribute to the development of dyslipidemia. Therefore, the effects of the Pro12Ala polymorphisms of the PPARgamma-2 gene on lipid metabolism were measured in 476 elderly persons whose birth weight was known. The Ala12 allele was associated with increased serum total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol concentrations but only among those who had birth weights below 3000 g. These interactions between the effects of the PPARgamma-2 gene on adult traits and the effects of birth weight may be interpreted as examples of gene-environmental interactions, which underlie plasticity during development.

Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on long-term body weight change in Finnish type 2 diabetic and non-diabetic control subjects.

OBJECTIVE: To investigate the independent and combined effects of the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3AR) gene and the (-3826) A-->G polymorphism of the uncoupling protein 1 (UCP1) gene on body weight change in type 2 diabetic and non-diabetic control subjects during a 10y follow-up study. DESIGN: Controlled 10y follow-up study with baseline, 5 and 10y examinations. SUBJECTS: 70 newly diagnosed, middle-aged type 2 diabetic patients and 123 non-diabetic control subjects from eastern Finland. MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and HbA1c. Genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS: No significant differences were found in the frequencies of the two polymorphisms between diabetic and control subjects. The polymorphisms were not cross-sectionally or longitudinally associated with body weight or BMI in diabetic or control subjects. When the diabetic and control subjects were analysed together, the change in the mean body weight was significantly greater among the subjects with both polymorphisms (n = 11) than among those with no polymorphisms (n = 103; change in weight 6.5 +/- 2.5% vs -0.2 +/- 0.8%, P=0.036, and change in Body Mass Index 8.5 +/- 2.6% vs 2.0 +/- 0.8%, P= 0.060, mean +/- s.e.m.). CONCLUSIONS: The simultaneous existence of the two polymorphisms was associated with a tendency to gain weight suggesting a synergistic effect of these polymorphisms on body weight gain.

Effect of a three-amino acid deletion in the alpha2B-adrenergic receptor gene on long-term body weight change in Finnish non-diabetic and type 2 diabetic subjects.

BACKGROUND AND OBJECTIVE: The short form (Glu9/Glu9) of the 12Glu9 deletion polymorphism of the alpha2B-adrenergic receptor gene was previously found to be associated with reduced basal metabolic rate in obese subjects. We investigated the effects of this polymorphism on changes in body weight in Finnish non-diabetic and type 2 diabetic subjects during a 10 y follow-up. DESIGN: Controlled 10 y follow-up study with baseline, 5 and 10 y examinations. SUBJECTS: A total of 126 non-diabetic control subjects and 84 newly diagnosed, middle-aged type 2 diabetic patients from eastern Finland participated. MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and glycosylated hemoglobin A1c. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis. RESULTS: No significant differences were found in the prevalence of the 12Glu9 deletion polymorphism between non-diabetic and type 2 diabetic subjects. The non-diabetic subjects with the Glu9/Glu9 genotype had a greater increase in their mean body weight during 5 y follow-up than the non-diabetic subjects with other genotypes (changes in body weight 0.4+/-5.7, -0.5+/-6.4 and 3.4+/-4.9% for the Glu12/Glu12, Glu12/Glu9 and Glu9/Glu9 genotypes, respectively, P=0.040 for the difference between the groups). Also, the trend for the increment of body weight was statistically significant in the non-diabetic subjects with the Glu9/Glu9 genotype (P=0.012). The 12Glu9 polymorphism was not cross-sectionally or longitudinally associated with body weight in type 2 diabetic subjects. CONCLUSIONS: The genotype of two short alleles (Glu9/Glu9) was associated with an increase in body weight among non-diabetic subjects.

Variation in the fatty acid binding protein 2 gene is not associated with markers of metabolic syndrome in patients with coronary heart disease.

BACKGROUND AND AIM: It has been suggested that the threonine (Thr) 54 allele of the intestinal fatty acid binding protein 2 (FABP2) gene is associated with insulin resistance and affects the fatty acid composition of serum lipids. Our aim was to investigate the frequency of the alanine (Ala) 54Thr polymorphism of the FABP2 gene in patients with coronary heart disease (CHD), and the association between the polymorphism and the markers of metabolic syndrome, serum lipid levels and the fatty acid profile of serum lipids. METHODS AND RESULTS: A total of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross-sectional EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) Study. Markers of metabolic syndrome included fasting plasma glucose concentration, serum high-density lipoprotein cholesterol and triglycerides (TG), waist circumference, the waist/hip ratio, body mass index (BMI) and blood pressure (BP). The frequency of the Thr54 allele was similar in the CHD patients (27.2%) and control subjects from two independent studies (27.8% and 28.7%). There were no significant differences in plasma glucose, serum lipids, BP, BMI, waist circumference or waist/hip ratio among the genotypes. Genotype frequency was not associated with the prevalence of diabetes or metabolic syndrome, but metabolic syndrome (as defined by National Cholesterol Education Program criteria) tended to be more frequent in subjects with the Thr/Thr genotype (p = 0.095). There were no differences in the fatty acid profiles of serum cholesteryl esters, TG or phospholipids among the genotypes. CONCLUSIONS: The Ala54Thr polymorphism of the FABP2 gene is not associated with CHD, markers of the metabolic syndrome, or the fatty acid profile of serum lipids in Finnish CHD patients.