Gene polymorphisms of desaturase enzymes of polyunsaturated fatty acid metabolism and adiponutrin and the increased risk of nonalcoholic fatty liver disease Manvi Vernekar a , Deepak Amarapurkar b , Kalpana Joshi c , Rekha Singhal a, ⁎ a Food Engineering and Technology Department, Institute of Chemical Technology, Mumbai, India b Department of Gastroenterology, Bombay Hospital and Medical Research Centre, Mumbai, India c Department of Biotechnology, Sinhgad College of Engineering, University of Pune, Pune, India abstract article info Article history: Received 25 July 2016 Accepted 19 August 2016 Available online xxxx 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 polymor- phisms 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 poly- morphism. 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 geno- types 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 polymor- phisms with NAFLD. It also verified the previously established association of rs738409 polymorphism with NAFLD. © 2016 Published by Elsevier B.V. Keywords: rs3834458 SNP PUFA metabolism PNPLA3 1. Introduction Nonalcoholic fatty liver disease (NAFLD) by definition is the accu- mulation of lipids (mainly triglycerides) in the liver without a signifi- cant history of alcohol consumption (Marchesini et al., 2003). NAFLD is a spectrum ranging from simple hepatic steatosis to steatohepatitis to ultimately cirrhosis and in a few cases hepatocellular carcinoma (Hazlehurst and Tomlinson, 2013). Prevalence of NAFLD varies from 10 to 40% worldwide while that in India ranges from 5 to 28% (Amarapurkar et al., 2007). NAFLD is considered to be the hepatic man- ifestation of metabolic syndrome (MetS). It is a multisystem disease and is projected to be one of the most common cause of chronic liver disease in the developed as well as developing nations (Byrne and Targher, 2015; Masuoka and Chalasani, 2013). Pathophysiology of NAFLD revolves around complex mechanisms like insulin resistance, central obesity, inflammation, dietary pattern as well as genetics (Zivkovic et al., 2007). Oxidative stress is one of the key modulator that governs NAFLD progression. Increased oxidative stress is independently associated with NAFLD in Asian Indians (Narasimhan et al., 2010). NAFLD may be considered as a chronic in- flammatory condition which represents the pro-inflammatory status conferred by the MetS. (Misra et al., 2009; Moller and Kaufman, 2004). NAFLD is an independent risk factor for coronary artery disease (CAD) and has been postulated to be not only a marker but also an early mediator of cardiovascular disease (CVD) (Sun and Lü, 2011; Targher, 2007). Adiponutrin or patatin-like phospholipase domain containing protein-3 (PNPLA3) is a membrane bound protein carrying out various enzyme activities like acylglycerol o-acyltransferase, calcium Meta Gene xxx (2016) xxx–xxx Abbreviations: NAFLD, nonalcoholic fatty liver disease; MetS, metabolic syndrome; PUFAs, polyunsaturated fatty acids; CAD, coronary artery disease; CVD, cardiovascular disease; PNPLA3, patatin-like phospholipase domain containing protein-3; GWAS, ge- nome wide association studies; D6D, delta-6-desaturases; D5D, delta-5-desaturases; ACS, acute coronary syndrome; PCR, polymerase chain reaction; RFLP, restriction fragment length polymorphism; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase. ⁎ Corresponding author at: Food Engineering and Technology Department, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India. E-mail addresses: manviv8@gmail.com (M. Vernekar), amarapurkar@gmail.com (D. Amarapurkar), joshikalpana@gmail.com (K. Joshi), rsinghal7@rediffmail.com, rs.singhal@ictmumbai.edu.in (R. Singhal). MGENE-00240; No. of pages: 5; 4C: http://dx.doi.org/10.1016/j.mgene.2016.08.009 2214-5400/© 2016 Published by Elsevier B.V. Contents lists available at ScienceDirect Meta Gene journal homepage: www.elsevier.com/locate/mgene Please cite this article as: Vernekar, M., et al., Gene polymorphisms of desaturase enzymes of polyunsaturated fatty acid metabolism and adiponutrin and the increased risk of nonalc..., Meta Gene (2016), http://dx.doi.org/10.1016/j.mgene.2016.08.009