Vera Karamfilova1, Antoaneta Gateva2, Yavor Assyov3, Asen Alexiev4, Alexey Savov5, Nadejda Yaneva6, Irena Ivanova7, Radina Ivanova-Boyanova8, Raya Ivanova9, Zlatina Vlahova10, Ludmila Mateva11, Zdravko Kamenov12. 1. Clinic of Endocrinology and Metabolic Diseases, Alexandrovska University Hospital, Department of Internal Medicine, Medical University Sofia, Bulgaria. verakaramfilova@abv.bg. 2. Clinic of Endocrinology and Metabolic Diseases, Alexandrovska University Hospital, Department of Internal Medicine, Medical University Sofia, Bulgaria. tony_gateva@yahoo.com. 3. Clinic of Endocrinology and Metabolic Diseases, Alexandrovska University Hospital, Department of Internal Medicine, Medical University Sofia, Bulgaria. yavovian@abv.bg. 4. Clinic of Gastroenterology, St. Ivan Rilski University Hospital, Department of Internal Medicine, Medical University Sofia, Bulgaria. assenalexiev@abv.bg. 5. National Genetic Laboratory, University Hospital of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Medical University Sofia, Bulgaria. alexey.savov@abv.bg. 6. National Genetic Laboratory, University Hospital of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Medical University Sofia, Bulgaria. nadeyaneva@gmail.com. 7. Clinical Laboratory Department, St. Ivan Rilski University Hospital, Medical University Sofia, Bulgaria. irena.dimitrova@gmail.com. 8. Laboratory of Clinical Pathology, Department of Endocrinology, Medical University Sofia, St. Ivan Rilski University Hospital, Sofia, Bulgaria. radinaivanova@abv.bg. 9. Clinic of Cardiology, Alexandrovska University Hospital, Department of Internal Medicine, Medical University Sofia, Bulgaria. raiaivanova@abv.bg. 10. Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria. zlati_vlahova@abv.bg. 11. Clinic of Gastroenterology, St. Ivan Rilski University Hospital, Department of Internal Medicine, Medical University Sofia, Bulgaria. lucymateva@yahoo.com. 12. Clinic of Endocrinology and Metabolic Diseases, Alexandrovska University Hospital, Department of Internal Medicine, Medical University Sofia, Bulgaria. zkamenov@hotmail.com.
Abstract
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. METHODS: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. RESULTS: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). CONCLUSIONS: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.
BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLDpatients with and without prediabetes. METHODS: A total of 208 obese NAFLDpatients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. RESULTS: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). CONCLUSIONS:PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obesepatients with NAFLD.
Authors: Omnia Aly; Hanan Hassan Zaki; Mohamed R Herzalla; Ahmed Fathy; Nermin Raafat; Mohamed M Hafez Journal: PLoS One Date: 2020-06-16 Impact factor: 3.240