Anti-FADS1 monoclonal antibody, clone 3E0

Nonalcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome (MetS). Adiponutrin gene polymorphisms have been associated with NAFLD worldwide. Polyunsaturated fatty acids (PUFAs) have been studied to have anti-inflammatory effects and plasma lipid lowering properties. PUFAs are endogenously synthesized with the help of delta-6-desaturase and delta-5-desaturase enzymes. They are encoded by FADS2 and FADS1 genes respectively. Polymorphisms in FADS genes have been implicated in diseases associated with the MetS like acute coronary syndrome and coronary artery disease. This is the first study aimed at investigating the association of FADS gene polymorphisms with NAFLD. Additionally, we confirm the association of adiponutrin gene polymorphism with NAFLD in Asian Indians. Single nucleotide polymorphisms of FADS2 rs3834458 and rs66698963, FADS1 rs174547 and adiponutrin gene rs738409 were analyzed. Two hundred and thirty patients were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Logistic regression was carried out to determine the association of genotypes with disease status after adjusting for confounding variables. It was observed that T/del, del/del genotypes of rs383445; I/D, D/D genotypes of rs66698963 and C/C, C/G genotypes of rs738409 were significantly associated with NAFLD. After adjusting for confounders, rs3834458 T/del and G/G minor allele carriers of rs738409 were found to increase the risk of NAFLD significantly. In conclusion, this study showed a novel association of FADS2 gene polymorphisms with NAFLD. It also verified the previously established association of rs738409 polymorphism with NAFLD. (C) 2016 Elsevier B.V. All rights reserved.

Background: The long-term role of fatty acids (FAs) in the cause of diabetes remains largely unclear. Objective: We aimed to investigate erythrocyte membrane FAs, desaturase activity, and dietary FAs in relation to the incidence of type 2 diabetes. Design: We applied a nested case-cohort design (n = 2724, including 673 incident diabetes cases) within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study, which involves 27,548 middle-aged subjects. Thirty erythrocyte membrane FAs (percentage of total FAs) and FA intake (percentage of total fat) were measured at baseline, and physician-confirmed incident diabetes was assessed during a mean follow-up of 7.0 y. We evaluated Delta(5) desaturase (D5D) and Delta(6) desaturase (D6D) activity by using FA product-to-precursor ratios (traditional approach) and by investigating variants in FADS1 and FADS2 genes that encode these desaturases (Mendelian randomization approach). Results: As a main finding, erythrocyte 16:1n27 and 18:3n26 and FA ratios, which reflect stearoyl coenzyme A desaturase (SCD) and D6D activity, were directly related to diabetes risk in multivariable-adjusted models [relative risks (95% CIs) comparing extreme quintiles: 16:1n27, 2.11 (1.46, 3.05); 18:3n26, 2.00 (1.38, 2.88); SCD, 2.61 (1.75, 3.89); and D6D, 2.46 (1.67, 3.63)], whereas the FA ratio that reflects D5D activity was inversely associated with risk [0.46 (0.31, 0.70)]. The Mendelian randomization approach corroborated the direct relation for D6D activity and tended to support the inverse relation for D5D activity. Proportions of dietary FAs showed only modest to low correlations with erythrocyte FAs and were not significantly associated with risk. Conclusion: The FA profile of erythrocyte membrane phospholipids and activity of desaturase enzymes are strongly linked to the incidence of type 2 diabetes. Am J Clin Nutr 2011;93:127-42.