The association between fat mass and obesity‐associated ( FTO ) genotype and serum vitamin D level in breast cancer patients

Abstract: The preventive effect of vitamin D against breast cancer can be influenced by gene polymorphisms. This study aimed to investigate the association between serum level of 25(OH) vitamin D and FTO genotype in breast cancer patients. A cross‐sectional study was carried out on 180 newly diagnosed patients with breast cancer in Tehran, Iran. The blood samples were collected from the participants in order to assess the FTO gene rs9939609 polymorphism by the tetra‐primer amplification refractory mutation system (Tetra‐ARMS) PCR method. The serum level of 25(OH) vitamin D was measured using the direct competitive enzyme‐linked immunosorbent assay (ELISA) method. The association between vitamin D and the FTO genotype in patients with breast cancer was assessed after adjustment for cofounders. The frequency of TT, AT and AA genotypes in the breast cancer patients were 43% (n = 77), 49% (n = 89) and 8% (n = 14), respectively. All patients with higher than 40 ng/dl of serum 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele (p = 0.019). No linear association was found between the number of FTO risk allele and the level of serum vitamin D. All patients with high serum level of 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele. FTO gene polymorphisms may counteract the beneficial effects of vitamin D in breast cancer prevention. Further studies can help to better understand the genetic factors predisposing to breast cancer and their effect on the association between vitamin D and breast cancer

The Association of Fat-Mass-and Obesity-Associated Gene Polymorphism (rs9939609) With Colorectal Cancer: A Case-Control Study

Background and Aim: The association between the rs9939609 polymorphism of fat mass and obesity-associated gene (FTO) and risk of colorectal cancer is controversial. This study aims to evaluate the relationship between FTO rs9939609 polymorphism and colorectal cancer (CRC) in Iranian people. Methods: A case-control study was conducted on 125 patients with CRC and 250 healthy subjects in Tehran, Iran. Demographic data and blood samples were collected from all participants. Genotyping of rs9939609 polymorphism was performed by the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. Results: The occurrence of AA genotype of FTO rs9939609 polymorphism in the colorectal cancer patients was significantly higher compared to that of healthy subjects (16.4 vs. 2.9%, respectively, P=0.02). The association between the frequency of risk allele of the FTO polymorphism and CRC (B=1.67, P=0.042) remained significant after adjustment for age. Further adjustment for gender (model 2) and marital status (model 3) did not change this result (B=1.67, P= 0.042 and B=1.67, P=0.043, respectively). The results remained significant after additional adjustment for ethnicity (B=1.57, P= 0.047). Conclusion: We found a positive association between the A allele of the rs9939609 polymorphism and CRC. Future studies are required to identify the underlying mechanisms

Efficacy of a Comprehensive Weight Reduction Intervention in Male Adolescents With Different FTO Genotypes

Background: The FTO gene polymorphisms may influence the effects of lifestyle interventions on obesity. The present study aimed to assess the influence of the rs9930506 FTO gene polymorphism on the success of a comprehensive weight loss intervention in male adolescents with overweight and obesity. Methods: This study was carried out on 96 adolescent boys with overweight and obesity who were randomly assigned to the intervention (n = 53) and control (n = 43) groups. The blood samples of the participants were collected, and the FTO gene was genotyped for the rs9930506 polymorphism. A comprehensive lifestyle intervention including changes in diet and physical activity was performed for 8 weeks in the intervention group. Results: Following the lifestyle intervention, BMI and fat mass decreased significantly in the intervention group compared with the control group (both p < 0.05), while no change was found in weight, height or body muscle percentage between the groups. The participants in the intervention group with the AA/AG genotype and not in carriers of the GG genotype had a significantly higher reduction in BMI (−1.21 vs. 1.87 kg/m2, F = 4.07, p < 0.05) compared with the control group. Conclusion: The intervention in individuals with the AA/AG genotype has been significantly effective in weight loss compared with the control group. The intervention had no association effect on anthropometric indices in adolescents with the GG genotype of the FTO rs9930506 polymorphism. Trial Registration: Name of the registry: National Nutrition and Food Technology Research Institute; Trial registration number: IRCT2016020925699N2; Date of registration: 24/04/2016; URL of trial registry record: https://www.irct.ir/trial/2144

Macronutrients and the FTO gene expression in hypothalamus; a systematic review of experimental studies

The various studies have examined the relationship between FTO gene expression and macronutrients levels. In order to obtain better viewpoint from this interactions, all of existing studies were reviewed systematically. All published papers have been obtained and reviewed using standard and sensitive keywords from databases such as CINAHL, Embase, PubMed, PsycInfo, and the Cochrane, from 1990 to 2016. The results indicated that all of 6 studies that met the inclusion criteria (from a total of 428 published article) found FTO gene expression changes at short-term follow-ups. Four of six studies found an increased FTO gene expression after calorie restriction, while two of them indicated decreased FTO gene expression. The effect of protein, carbohydrate and fat were separately assessed and suggested by all of six studies. In Conclusion, The level of FTO gene expression in hypothalamus is related to macronutrients levels. Future research should evaluate the long-term impact of dietary interventions

CREB-binding protein (CREBBP) and preeclampsia: a new promising target gene

Preeclampsia (PE) is a major complication of pregnancy and remains a leading cause of neonatal and maternal mortality worldwide. Several studies have revealed that the incidence of preeclampsia is high in mothers who carried a fetus with Rubinstein-Taybi Syndrome due to the mutation in CREBBP. We aimed to compare the expression level of the CERBBP gene between preeclamptic and healthy placenta in our study. The expression level of CREBBP gene was evaluated in a total of one hundred placental biopsies from PE patients and healthy pregnant women after delivery using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the differential expression of CREBBP was assessed between the maternal and fetal sides of the placenta. Expression of the CREBBP gene was higher in preeclampsia patients compared with the controls (Fold change = 2.158; P = 0.018). Moreover, the gene expression was slightly higher in the fetal side of the placenta, although it was not significantly different (Fold change = 1.713, P = 0.254). Our findings show a role for CREBBP in the pathogenesis of PE. Due to the important role of CREBBP in angiogenesis and hypoxia, the gene may serve as a promising target in future studies

The obesity associated FTO gene polymorphism and the risk of preeclampsia in Iranian women: A case–control study

Background Preeclampsia (PE) is one of the leading disorders in pregnant women with maternal and fetal complications. Obesity is considered an important risk factor for the development of PE. Genetic variations in fat mass and obesity associated (FTO) gene may play a role in the development of PE. This study aimed to investigate the possible association between FTO gene rs9939609 and PE risk in a sample of Iranian pregnant women. Material and methods In this case–control study, 312 pregnant women were included, including 128 with PE and 184 without PE. Demographic data and blood samples were obtained from all individuals. The genotyping of rs9939609 polymorphisms was performed by the tetra‐primer amplification refractory mutation system‐polymerase chain reaction (TP‐ARMS‐PCR) method, and the results of TP‐ARMS‐PCR were confirmed using DNA sequencing. Results The genotype frequency was 50%, 47.7%, and 2.3% in pregnant patients and 37%, 47.8%, and 15.2% in healthy controls for TT, AT, and AA, respectively. The risk of PE was significantly reduced in the pregnant women having the AA genotype. Conclusion Based on the results of the present study, rs9939609 polymorphism in the FTO gene may play a protective role against PE. However, further studies are warranted

The effect of FTO gene rs9939609 polymorphism on the association between colorectal cancer and different types of dietary fat intake: a case-control study

Abstract Background Colorectal cancer (CRC) is one of the most common cancers in the world. Some dietary factors such as fat intake have been identified as the risk factors for CRC. This study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene rs9939609 polymorphism on the association between CRC and different types of dietary fats. Methods This case-control study was performed on 135 CRC cases and 294 healthy controls in Tehran, Iran. Data on demographic factors, anthropometric measurements, physical activity, the intake of different types of dietary fats, and FTO gene rs9939609 polymorphism was collected from all participants. The association between cancer and dietary fat intake in individuals with different FTO genotypes was assessed using different models of logistic regression. Results Oleic acid intake was higher in the case group compared to the control group in both people with TT (7.2±3.46 vs. 5.83±3.06 g/d, P=0.02) and AA/AT genotypes (8.7±6.23 vs. 5.57 ±3.2 g/d, P<0.001). Among carriers of AA/AT genotypes of FTO rs9939609 polymorphism, a positive association was found between CRC and higher intakes of oleic acid (OR=1.12, CI95% 1.03–1.21, P=0.01) and cholesterol (OR=1.01, CI95% 1.00–1.02; P=0.01) after adjusting for age, sex, physical activity, alcohol use, smoking, calorie intake, and body mass index. Conclusion Higher intakes of cholesterol and oleic acid were associated with a higher risk of CRC in FTO-risk allele carriers. The association of CRC and dietary fat may be influenced by the FTO genotype. Further longitudinal studies are warranted to confirm these findings

Interactions between macro-nutrients’ intake, FTO and IRX3 gene expression, and FTO genotype in obese and overweight male adolescents

Abstract This study is the first to identify the effects of FTO genotype on the interactions between the level of macro-nutrients intake and the expression level of fat mass and obesity associated (FTO) and homeobox transcription factor iriquois-3 (IRX3) genes This longitudinal study was carried out on 84 overweight and obese adolescent boys in Tehran, Iran. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in PBMCs and macro-nutrients’ intake were assessed at baseline and after 18 weeks of the intervention. The results identified that the higher carbohydrates intake significantly up-regulated the FTO gene (P = 0.001) and down-regulated the IRX3 gene (P = 0.01). Protein intake up-regulated the FTO gene (P = 0.001). In carriers of GG genotype of FTO gene, the amount of dietary carbohydrate had a positive association with FTO gene expression (p = 0.001, and p = 0.04, respectively). In AA/AG carriers, dietary protein was positively associated with FTO gene expression (p = 0.001) and dietary carbohydrate was negatively associated with IRX3 gene expression (P = 0.04). Therefore, dietary carbohydrateseems to be associated with FTO and IRX3 genes expression. These associations are influenced by FTO genotype