Drug Metabol Pers Ther 2018; aop Branko Srećković*, Ivan Soldatovic, Emina Colak, Igor Mrdovic, Mirjana Sumarac-Dumanovic, Hristina Janeski, Nenad Janeski, Jasna Gacic and Vesna Dimitrijevic-Sreckovic Homocysteine is the confounding factor of metabolic syndrome-confirmed by siMS score https://doi.org/10.1515/dmpt-2017-0013 Received March 30, 2017; accepted February 9, 2018 Abstract Background: Abdominal adiposity has a central role in developing insulin resistance (IR) by releasing pro-inflam- matory cytokines. Patients with metabolic syndrome (MS) have higher values of homocysteine. Hyperhomocysteine- mia correlates with IR, increasing the oxidative stress. Oxidative stress causes endothelial dysfunction, hyper- tension and atherosclerosis. The objective of the study was to examine the correlation of homocysteine with siMS score and siMS risk score and with other MS co-founding factors. Methods: The study included 69 obese individuals (age over 30, body mass index [BMI] >25 kg/m 2 ), classified into two groups: I-with MS (33 patients); II-without MS (36 patients). Measurements included: anthropometric parameters, lipids, glucose regulation parameters and inflammation parameters. IR was determined by homeo- static model assessment for insulin resistance (HOMA- IR). ATP III classification was applied for diagnosing MS. SiMS score was used as continuous measure of metabolic syndrome. Results: A significant difference between groups was found for C-reactive protein (CRP) (p < 0.01) apolipoprotein (Apo) B, HOMA-IR and acidum uricum (p < 0.05). siMS risk score showed a positive correlation with homocysteine (p = 0.023), while siMS score correlated positively with fibrinogen (p = 0.013), CRP and acidum uricum (p = 0.000) and homocysteine (p = 0.08). Homocysteine correlated pos- itively with ApoB (p = 0.036), HbA 1c (p = 0.047), HOMA-IR (p = 0.008) and negatively with ApoE (p = 0.042). Conclusions: Correlation of siMS score with homocyst- eine, fibrinogen, CRP and acidum uricum indicates that they are co-founding factors of MS. siMS risk score corre- lation with homocysteine indicates that hyperhomocyst- einemia increases with age. Hyperhomocysteinemia is linked with genetic factors and family nutritional scheme, increasing the risk for atherosclerosis. Keywords: atherosclerosis; homocysteine; insulin resist- ance; metabolic syndrome; obesity. Introduction Homocysteine (HCY) is an essential amino acid gener- ated in methionine metabolism and it is found in the food proteins. There are two types of hyperhomocysteinaemia. First type is rare form due to genetic variant, methylene- tetrahydrofolatereductase (MTHFR) that impairs ability to process folate. MTHFR is an enzyme, which catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, circulating form of folate. The MTHFR gene has at least two functional polymorphisms, 677T and 1298A [1]. The MTHFR 677T polymorphism is associated with reduced enzymatic activity, decreased concentrations of folate in serum, plasma and red blood cells, and increased plasma HCY concentrations. The MTHFR polymorphism 1298A also affects MTHFR activ- ity but is not associated with higher plasma HCY or lower folate levels. The second type is more common form, related to nutritional factors, presented in moderately elevated HCY levels. Low intake of folic acid, vitamin B12 and vitamin B6 correlate with elevated HCY levels independently of any genetic mutation [2]. Furthermore, renal and thyroid dysfunction, diabetes and cancer may be associated with moderately elevated HCY levels. Lastly, alcohol, tobacco and coffee consumption, as well as older age and menopause, are related to elevated HCY *Corresponding author: Dr. Branko Srećković, MSc, Clinical Center Bežanijska Kosa, 11000 Belgrade, Serbia, Phone: +381 692 667 721, E-mail: drsreckovic65@gmail.com Ivan Soldatovic: Institute for Medical Statistics and Informatics, Belgrade, Serbia Emina Colak: Institute of Medical Biochemistry, Clinical Center of Serbia, Belgrade, Serbia Igor Mrdovic: Clinic for Cardiovascular Diseases, Emergency Center, Belgrade, Serbia Mirjana Sumarac-Dumanovic and Vesna Dimitrijevic-Sreckovic: Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia Hristina Janeski: University Children’s Hospital, Belgrade, Serbia Nenad Janeski: Clinical Center Zemun, Belgrade, Serbia Jasna Gacic: Clinical Center Bežanijska Kosa, Belgrade, Serbia Brought to you by | Göteborg University - University of Gothenburg Authenticated Download Date | 4/7/18 8:04 PM