Evaluating the interaction of common FTO genetic variants, added sugar, and trans-fatty acid intakes in altering obesity phenotypes.

BACKGROUND AND AIMS: The results of studies on the effect of trans-fatty acids (TFAs) and added sugars on obesity are not consistent. This study aimed to investigate whether the association of changes in general and central obesity with added sugar and TFA intakes is modified by common fat mass and obesity-associated gene (FTO) polymorphisms, in isolation or in a combined-form genetic risk score (GRS). METHODS AND RESULTS: Subjects of this cohort study were selected from among adult participants of the Tehran Lipid and Glucose Study (n = 4292, 43.2% male). Dietary data were collected using a valid and reliable food frequency questionnaire. The genotypes of selected polymorphisms (rs1421085, rs1121980, and rs8050136) were determined. Genetic risk score (GRS) was calculated using the dominant weighted method. The mean age of participants was 42.6 ± 14 and 40.4 ± 13 years in men and women, respectively. FTO rs8050136 polymorphisms and TFAs have a significant interaction in changing body mass index (BMI) (P interaction = 0.01). There were no changes in waist circumference (WC) and BMI among FTO risk allele carriers, across quartiles of added sugar intake. GRS and TFA intakes significantly interacted in altering the BMI and WC; thus, a higher intake of TFAs was associated with higher changes of BMI and WC in subjects with high GRS (P trend<0.05) compared to individuals with low GRS. CONCLUSION: Our findings suggest that TFA intake can increase the genetic susceptibility of FTO SNPs to BMI or WC change.

Effect of interactions of polymorphisms in the Melanocortin-4 receptor gene with dietary factors on the risk of obesity and Type 2 diabetes: a systematic review.

AIM: To perform a systematic review of the effect of interaction between Melanocortin-4 receptor (MC4R) single nucleotide polymorphisms and diet on the development of obesity and Type 2 diabetes. BACKGROUND: Environmental factors, such as nutrient intakes or feeding behaviours, can modulate the association of polymorphism in the MC4R gene with obesity and Type 2 diabetes mellitus. METHODS: A systematic literature search was conducted in the PubMed, Scopus and Google Scholar databases, with a combination of the following keywords: Diet*, nutr*, melanocortin receptor, melanocortin 4 receptor and MC4R. To assess the quality of observational studies, we used a 12-item quality checklist, derived from the STREGA statement. RESULTS: A total of 14 articles were selected based on the inclusion and exclusion criteria. Consumption of highly salty foods and adherence to a Mediterranean dietary pattern can modulate the association between MC4R polymorphisms and the risk of obesity or Type 2 diabetes. Despite the highly contradictory results of intervention studies, after short-term lifestyle interventions, children with variant alleles of MC4R single nucleotide polymorphisms can lose more body weight, compared with non-carriers, although they may have difficulty in maintaining this weight loss in the long-term. To interpret the results of studies on adults, we need further studies. CONCLUSIONS: The interaction between MC4R genes with dietary factors plays a significant role in the development of obesity or Type 2 diabetes phenotypes. Early detection of MC4R risk alleles in individuals and modification of their diet based on these results could be an efficient strategy to prevent obesity or diabetes in these subgroups.

Association between TNF-α promoter G-308A and G-238A polymorphisms and obesity.

Tumor necrosis factor-α (TNF-α), an adipokine, is produced in adipocytes, and the elevation of its levels has been linked to obesity and insulin resistance in some population. In this study the relationship between TNF-α promoter gene polymorphism and obesity in an Iranian population has been studied. Subjects were randomly selected from Tehran Cohort Lipid and Glucose Study. Adult participants placed in three groups according to their body mass index (BMI): BMI < 25, 25 ≤ BMI < 30, BMI ≥ 30 and under-18 subjects placed in two groups, under 85th percentile BMI and above 85th percentile. Finally, 244 persons were selected for G-308A and G-238A polymorphisms analysis. The FBS, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, cholesterol levels and blood pressure and HOMA of all subjects were measured. The polymorphism -308 and -238 were revealed by restriction fragment length polymorphism (RFLP; NCOI and MSPI) after the promoter site was amplified by PCR. The allele frequency of TNF-α polymorphism was in the Hardy-Weinberg equilibrium. There was no relation between BMI and the frequency of this allele. The fact that there is no association between G-308A and G-238A TNF-α promoter polymorphisms and obesity probably shows that it is not an important risk factor for obesity and consequently for cardiovascular disease.

Association of body mass index and Trp64Arg polymorphism of the beta3-adrenoreceptor gene and leptin level in Tehran Lipid and Glucose Study.

In this study the association between beta3-adrenoceptor gene polymorphism and serum concentration of leptin with body mass index (BMI) is investigated. Using subjects in the Tehran Lipid and Glucose Study, genotyping of the Trp64Arg polymorphism of the beta3-adrenoreceptor gene was performed using a restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique was used and the association with obesity was investigated. At total of 197 men and 204 women were divided into four groups (BMI<20, 20< or =BMI<25, 25< or =BMI<30, BMI< or =30) and 97, 98, 104 and 102 subjects, respectively, were placed randomly in the four groups. Leptin level was determined by an enzyme immunoassay (EIA) method and FBS, HDL-C, triglyceride and total cholesterol levels were determined by an enzyme colorimetric method. Body mass index (BMI) was also measured. The A (Arg) allele frequency was 0.08 among the population and its presence was significantly associated with increase of leptin level (AA/TA, 30.5+/-24.8 ng/mL; TT, 22.6+/-20.9 ng/mL; P=0.014) but there was no significant association with increased BMI (AA/TA, 27+/-5.6 kg/m2; TT, 25.4+/-5.5 kg/m2; P=0.072). These data show that the presence of the Arg64 allele at the beta3-adenoceptor gene locus is related to increase in leptin level in this population, but is not related to body mass index.