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A novel polymorphism in the fatty acid desaturase 2 gene (Fads2): A possible role in the basal metabolic rate.

ABSTRACT: Fatty acyl composition of cell membrane lipids, particularly the abundance of highly unsaturated docosahexaenoic fatty acid (22:6n-3, DHA), is likely to be an important predictor of basal metabolic rate (BMR). Our study was performed using two lines of laboratory mice divergently selected for either high or low BMR. We describe a novel single nucleotide polymorphism in the Fads2 gene encoding ?6-desaturase, a key enzyme in the metabolic pathways of polyunsaturated fatty acids (PUFAs). The allele frequencies of Fads2 were significantly different in both lines of mice. The analysis of genetic distances revealed that the genetic differentiation between the two studied lines developed significantly faster at the Fads2 locus than it did at neutral loci. Such a pattern suggests that the Fads2 polymorphism is related to the variation in BMR, i.e. the direct target of selection. The Fads2 polymorphism significantly affected abundance of several PUFAs; however, the differences in PUFA composition between lines were compatible with the difference in frequency of Fads2 alleles only for DHA. We hypothesize that the polymorphism in the Fads2 gene affects the BMR through modification of DHA abundance in cell membranes. This may be the first example of a significant link between a polymorphism in a gene responsible for fatty acyl composition and variation in BMR.

SUBMITTER: Czajkowska M

PROVIDER: S-EPMC6394981 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A novel polymorphism in the fatty acid desaturase 2 gene (Fads2): A possible role in the basal metabolic rate.

Czajkowska Magdalena M Brzęk Paweł P Dobrzyń Paweł P

PloS one 20190228 2

Fatty acyl composition of cell membrane lipids, particularly the abundance of highly unsaturated docosahexaenoic fatty acid (22:6n-3, DHA), is likely to be an important predictor of basal metabolic rate (BMR). Our study was performed using two lines of laboratory mice divergently selected for either high or low BMR. We describe a novel single nucleotide polymorphism in the Fads2 gene encoding Δ6-desaturase, a key enzyme in the metabolic pathways of polyunsaturated fatty acids (PUFAs). The allele ...[more]

PMID: 30818386

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Project description:BackgroundRecent studies have shown that dietary intakes and gene variants have a critical role in the obesity related comorbidities. This study aimed to evaluate the effects of the interactions between Fatty acid desaturase 2 (FADS2) gene rs174583 polymorphism and two dietary indices on cardiometabolic risk factors.MethodsThis cross-sectional study was carried out on 347 obese adults aged 20-50 years old in Tabriz, Iran. Healthy eating index (HEI) and Diet quality index-international (DQI-I) were evaluated by a validated semi-quantitative 147-item Food frequency questionnaire (FFQ). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine FADS2 gene variants. Multivariate analysis of covariance (MANCOVA) was used to identify gene-diet interactions on metabolic parameters.ResultsWaist circumference (WC) and serum triglyceride (TG) levels were significantly higher among carriers of TT genotype of FADS2 gene (P < 0.05). In addition, the interactions between FADS2 gene rs174583 polymorphism and DQI-I had significant effects on weight (P interaction = 0.01), fat mass (P interaction = 0.04), fat free mass (P interaction = 0.03), and Body mass index (BMI) (P interaction = 0.02); the highest level of these parameters belonged to TT carriers. Similarly, the interactions between FADS2 gene variants and HEI had significant effects on insulin (P interaction < 0.001), Homeostasis model assessment of insulin resistance (HOMA-IR) (P interaction < 0.001), Quantitative insulin check index (QUICKI) (P interaction = 0.001), and alpha Melanocyte stimulating hormone (α-MSH) (P interaction = 0.03).ConclusionIn this study, for the first time, we reported the effects of gene-diet interactions on metabolic traits. Compliance with dietary indices (DQI-I and HEI) ameliorated the adverse effects of gene variants on metabolic risk factors, especially in heterogeneous genotypes. Further prospective cohort studies are needed to confirm these results.

Project description:Background and Aim: Genetic variation in fatty acid desaturases (FADS) has previously been linked to several diet-related diseases. We aimed to determine whether the FADS2 rs174583 variant interacts with the Dietary Approach to Stop Hypertension (DASH) score and Mediterranean dietary score (MDS) to influence cardio-metabolic risk factors among obese adults. Methods: This cross-sectional study was performed among 347 apparently healthy obese adults (aged 20-50 years). Dietary quality indicator scores (DASH and MDS) were generated using a validated 147-item Food Frequency Questionnaire (FFQ). The FADS2 rs174583 variant was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The gene-diet interaction was analyzed by the ANCOVA multivariate interaction model. Results: A significant interaction was observed between rs174583 and adherence to the DASH score in relation to serum triglyceride (TG) concentration among the female group (P Interaction = 0.046); CT-genotype carriers who were assigned to the second tertile of DASH compared with those in the first tertile had a lower TG level (P < 0.05). Another significant interaction was revealed between adherence to MDS score and rs174583 polymorphism on serum glucose levels (P Interaction = 0.044); the lowest mean of glucose level was observed in homozygous minor subjects (TT) in the third tertile of MDS, in comparison with other tertiles of this dietary index (P < 0.05). There was a similar significant interaction between DASH and rs174583 in relation to diastolic blood pressure (P Interaction = 0.038) among the male group. Additionally, a significant positive association was found between TT genotype and odds of having high TG both in the crude (OR, 3.21; 95% CI, 1.02-10.14) and adjusted (OR, 3.58; 95% CI, 1.07-11.97) models, taking into account different confounders. Conclusion: Adherence to the dietary quality indicators (DASH and MDS) modified the relationship between FADS2 rs174583 polymorphism and cardio-metabolic risk factors in obese subjects. Prospective cohort studies are needed to confirm the results of our study.

Dataset Information

A novel polymorphism in the fatty acid desaturase 2 gene (Fads2): A possible role in the basal metabolic rate.

Publications

A novel polymorphism in the fatty acid desaturase 2 gene (Fads2): A possible role in the basal metabolic rate.

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