title: Polymorphisms of extrinsic death receptor apoptotic genes (FAS -670 G>A, FASL -844 T>C) in coronary artery disease.
abstract: Apoptosis plays an important role in atherogenesis and rupture of vulnerable plaques in coronary artery disease. FAS and FAS ligand (FASL) induce apoptosis when FAS binds to FAS-L. However sFas blocks apoptosis by binding to FAS and FASL or sFasL. The present study is sought to examine the role of extrinsic apoptotic genes (FAS, FASL) polymorphism and serum levels of FAS, FASL in the pathogenesis and susceptibility to CAD in south Indian population. The study included 300 CAD patients and 300 healthy controls. Lipid profiles, sFas, sFasL were estimated by commercially available kits. FAS -670 G>A, FASL -844 T>C genotypes were analyzed by PCR-RFLP. Secondary structures of pre mRNA were analyzed by the Vienna RNA webserver and gene-gene and gene-environment interactions were determined by MDR analysis. Total cholesterol, triglyceride and LDL levels were significantly high in CAD patients compared to the controls. Molecular analysis revealed that the frequency of the AA genotype of FAS (54% vs 27%) and CC genotypes of FASL (10.3% vs 1.3%) were high in CAD patients compared to controls. Secondary structure analysis of FAS and FASL confirmed our molecular analysis. sFas levels were low while serum sFasL were high in CAD patients. MDR analysis revealed synergistic effects of gene polymorphisms and additive effects of epidemiological factors on risk of CAD. Polymorphisms of FAS (-670 G/A), FASL (-844 T/C) and their circulating levels play an important role in the pathology of CAD.
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Telangana, 500 007, India.
authors.forename: G
authors.initials: G
authors.lastname: Kishore Kumar
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Telangana, 500 007, India.
authors.forename: G
authors.initials: G
authors.lastname: Rajesh Kumar
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Telangana, 500 007, India.
authors.forename: K
authors.initials: K
authors.lastname: Mrudula Spurthi
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Telangana, 500 007, India.
authors.forename: S
authors.initials: S
authors.lastname: Nivas
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Telangana, 500 007, India.
authors.forename: P
authors.initials: P
authors.lastname: Chiranjeevi
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Telangana, 500 007, India.
authors.forename: Altaf
authors.initials: A
authors.lastname: Ali
authors.affiliation: Durgabai Deshmukh Hospital and Research Center, Vidya Nagar, Hyderabad, Telangana, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Sahu
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Telangana, 500 007, India.
authors.forename: N
authors.initials: N
authors.lastname: Pratibha
authors.affiliation: Department of Genetics, Osmania University, Hyderabad, Telangana, 500 007, India. surekharanih@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Surekha Rani
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics*; D053222:Fas Ligand Protein / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019014:fas Receptor / Q000097:blood / Q000235:genetics*
chemical_list: D053222:Fas Ligand Protein; D008055:Lipids; D019014:fas Receptor
keywords: Apoptosis; CAD; FAS; FASL; Plaque rupture