Meta Gene 26 (2020) 100817 Available online 28 October 2020 2214-5400/© 2020 Elsevier B.V. All rights reserved. Folate metabolism: Impact of involved genetic variants on homocycteine and folate levels in type 2 diabetic patients with coronary artery disease Amal F. Gharib a, b , Khadiga A. Ismail a, c , Mohamed Arab d , Rasha L. Etewa e , Nermin Raafat b, * a Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia b Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt c Department of Medical Parasitology, Ain Shams Faculty of Medicine, Egypt d Cardiology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt e Pathology Department, College of Medicine, Jouf University, Sakaka, Saudi Arabia A R T I C L E INFO Keywords: MTHFR C677T RFC-1 A80G Hcy Folate T2DM CAD ABSTRACT Background: Type2 diabetes mellitus (T2DM) has severe impacts on quality of life throughout the world. Coro- nary artery disease (CAD) is one of the most serious microvascular complications of T2DM. Objective: To explore the relationship between plasma homocysteine (Hcy) and folate levels, and their related methylenetetrahydrofolate reductase (MTHFR) C677T and reduced folate carrier-1 (RFC-1) A80G genes poly- morphism in T2DM accompanied by CAD. Methods: This case-control study enrolled 120 T2DM patients, 60 of them had CAD, and 60 healthy control subjects. Plasma Hcy and folate were measured by ELISA and genotyping was performed by PCR-RFLP. Lipid profle was analyzed by spectrophotometer. Results: Plasma Hcy was increased and folate was decreased in both diabetic groups in relation to control group. T2DM with CAD showed signifcant difference with T2DM group. Hcy level was positively correlated with total cholesterol and triglycerides in T2DM and with LDL in T2DM with CAD patients. MTHFR TT and TC genotypes had signifcantly higher risk of CAD in T2DM. RFC-1 GG and AG genotypes were signifcantly higher in diabetic groups. Hcy was signifcantly higher and folate was lower in MTHFR677 TT + TC than that in CC genotype in T2DM with CAD. In RFC-1 GG + GA, Hcy level was higher and folate was lower than that of AA. Conclusion: MTHFR and RFC-1 genetic variants are associated with high Hcy and low folate levels in T2DM with CAD patients and are related to dyslipidemia. 1. Introduction Diabetes is a major metabolic disease that has a serious infuence on lives and well-being of the affected person, families, and societies worldwide. It is considered among topmost 10 causes of death in adults and around four million deaths were estimated worldwide in 2017 (International Diabetes Federation, 2017). Grounding on global, regional and national diabetic occurrence in 2009, International Diabetes Federation (IDF) estimated 285 million diabetes sufferers of both types of diabetes (International Diabetes Federation, 2009), increasing to 366, 382, 415, 425 and 463 million, in 2011 (International Diabetes Federation, 2011), 2013 (International Diabetes Federation, 2013), 2015 (International Diabetes Federation, 2015a), 2017 (International Diabetes Federation, 2017), 2019 (Saeedi et al., 2019) respectively. It is predicted that by 2030; 578 million people will have diabetes and the number will increase by 51% (700 million) in 2045 (Saeedi et al., 2019). Type 2 diabetes mellitus (T2DM) accounts for almost 90% of the total cases of diabetes. The socioeconomic status, sedentary lifestyle and increased life expectancy may explain this upsurge (Saeedi et al., 2019; DIAMOND Project Group, 2006). The reason of rising prevalence of T2DM remains unclear. Early detection of cases, improved diabetes management, long survival, and decreased in premature mortality (Saeedi et al., 2019) are additional contributes to increased diabetes Abbreviation list: CAD, Coronary artery disease; CVD, cardiovascular diseases; Hcy, homocysteine; IDF, International Diabetes Federation; LDL cholesterol, low density lipoprotein; MTHFR, methylenetetrahydrofolate reductase; RFC-1, reduced folate carrier-1; SLC19A1, solute carrier family 19 members 1; SNP, single nucleotide polymorphism; TG, triglyceride. * Corresponding author. E-mail address: nraafat@zu.edu.eg (N. Raafat). Contents lists available at ScienceDirect Meta Gene journal homepage: www.elsevier.com/locate/mgene https://doi.org/10.1016/j.mgene.2020.100817 Received 2 August 2020; Received in revised form 24 October 2020; Accepted 26 October 2020