title: Genetic basis of dyslipidemia in disease precipitation of coronary artery disease (CAD) associated type 2 diabetes mellitus (T2DM).
abstract: Type 2 diabetes mellitus (T2DM) and its complications are linked to environmental, clinical, and genetic factors. This review analyses the disorders of lipids and their genetics with respect to coronary artery disease (CAD) associated with T2DM. Cell organelles, hepatitis C-virus infection, reactive oxygen species produced in mitochondria, and defective insulin signaling due to the arrest of G1 phase to S phase transition of β-cells have significant roles in the precipitation of the diseases. Adiponectin is anti-inflammatory and anti-atherosclerotic and improves insulin resistance. Low-density lipoprotein (LDL) is atherosclerotic, and LDL-cholesterol in T2DM is associated with high-cardiovascular risk. Further, LDL cholesterol reduction significantly reduces cardiovascular morbidity and mortality. High-density lipoprotein (HDL) is also anti-atherosclerotic due to HDL associated paraoxonase-1 serum enzyme, which prevents LDL oxidative modifications and the development of CAD. Moreover, elevated apolipoprotein B and apolipoprotein A-I (ApoB/ApoA-I) ratio in plasma is also a risk factor for CAD. LDL receptor, adiponectin, and endocannabinoid receptor-1 genes are independently associated with CAD and T2DM. Polymorphism of Apo E2 (epsilon2) is a positive factor to increase the T2DM risk and Apo E4 (epsilon4) is a negative factor to reduce the disease risk. Taq 1B polymorphism of cholesterol ester transfer protein (CETP) gene contributes to the development of atherosclerosis, whereas haplotypes of APOA5, APOC3, APOC4, and APOC5 genes are in the same cluster and are independently associated with high plasma triglyceride level, CAD and T2DM. In conclusion, because various genes, LDLR, CETP, APOA5, Apo E, Apo B, and Apo A-I, are associated with the precipitation of CAD associated with T2DM, a personalized diet-gene intervention therapy may be advocated to reduce the disease precipitation.
authors.affiliation: Department of Computational Biology and Bioinformatics, Sam Higginbottom Institute of Agriculture, Technology and Sciences, Deemed to be University, Allahabad, India.
authors.forename: Resal
authors.initials: R
authors.lastname: Raj
authors.affiliation: Department of Biotechnology & Bioinformatics, SGGS College, Sector 26, Chandigarh, India.
authors.forename: Jasvinder Singh
authors.initials: JS
authors.lastname: Bhatti
authors.affiliation: Department of Endocrinology, PGIMER, Chandigarh, India.
authors.forename: Sanjay Kumar
authors.initials: SK
authors.lastname: Badada
authors.affiliation: Department of Biological Sciences, Sam Higginbottom Institute of Agriculture, Technology and Sciences, Deemed to be University, Allahabad, India.
authors.forename: Pramod W
authors.initials: PW
authors.lastname: Ramteke
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000235:genetics; D053329:Apolipoprotein E2 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001054:Apolipoproteins A / Q000235:genetics; D001056:Apolipoproteins C / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D050171:Dyslipidemias / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D006526:Hepatitis C / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012307:Risk Factors
chemical_list: C437704:APOA5 protein, human; C097349:APOC4 protein, human; D052242:Adiponectin; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001054:Apolipoproteins A; D001056:Apolipoproteins C; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017382:Reactive Oxygen Species; D043884:Receptor, Cannabinoid, CB1; D011973:Receptors, LDL; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: cardiovascular disease; dyslipidaemia; precipitation; reactive oxygen species