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|Title:||Selective Genetic Markers in Association with the Development of Coronary Heart Disease in the Kuwaiti Population||Authors:||فاطمة اسماعيل سالم غلوم||Supervisor:||د. سوزان البستان||Keywords:||Coronary Heart Disease the Kuwaiti||Issue Date:||2011||Publisher:||Kuwait university - college of graduate studies||Abstract:||iv Abstract Coronary heart disease (CHD) is one of the leading causes of death worldwide. CHD is a complex disorder with a multifactorial etiology that arises from failure at the gene or environmental level or interaction between the two. Several apolipoprotein gene polymorphisms including APOAV c.56C›G, APOB signal peptide and APOCIII 3238C›G have an influence on plasma lipids/lipoproteins metabolism resulting in accumulation of fatty deposits on the arterial wall and plaque formation, subsequently leading to CHD. In addition, several other candidate genes have been identified and documented to play major roles in regulating blood vessels including eNOS and ACE. Polymorphisms within these genes (eNOS 894G›T and ACE I/D) increase the risk to CHD in the presence of any of the known environmental risk factors. The present study attempted to provide a small insight on the association of selective genetic markers (APOAV c.56C›G, APOB signal peptide, APOCIII 3238C›G, eNOS 894G›T and ACE I/D) with developing CHD in the Kuwaiti population. In this study blood samples were obtained from a total of 735 Kuwaiti nationals including both CHD patients (n=375) and controls (n=363) that were selected and matched based on sex and age (± 2 years) and included 363 Kuwaiti nationals, who may have other types of diseases but not CHD. DNA extraction was carried out using a salting-out method. The genotyping methods used in this study involved AS-PCR for the APOB signal peptide and the ACE I/D polymorphism as well as TaqMan Real-Time PCR was employed for the APOAV c.56C›G, APOCIII 3238C›G and eNOS 894G›T polymorphisms. The genotyping products were used to construct the genetic profile for each sample. Statistical analysis including HWE, LD and logestic regression analysis were performed to determine the frequencies of the genotype and alleles, and to investigate the association of the five polymorphisms and the environmental risk factors of CHD in the Kuwaiti population. The statistical analysis of the known environmental risk factors data indicated that all studied medical histories were found to be significantly associated with CHD, in addition to ethnicity and cigarette smoking (P=0.00). Direct association was observed between APOAV c.56C›G, APOB signal peptide, eNOS 894G›T and ACE I/D polymorphisms, in terms of genotype and allele frequencies, with developing CHD in the Kuwaiti population, whereas APOCIII 3238C›G polymorphism showed no significant direct association. The studied APOCIII 3238C›G polymorphism was found to be in Hardy-Weinberg Equilibrium, while the rest of the polymorphisms were deviated within the CHD group, the controls, or both. Among the SNPs, CC genotype of the APOAV c.56C›G followed by the TT genotype of eNOS 894G›T contributed the highest risk for CHD, while smoking and positive medical history of diabetes mellitus were the strongest contributors among the known risk factors. The current study is the first one to perform extensive genetic markers analysis of CHD in the Kuwaiti population. The findings indicate that alleles and genotypes of the five selected polymorphisms independently may influence the development of CHD in the Kuwaiti population. Therefore, other polymorphisms and environmental factors should be investigated to understand the role of these genes in developing CHD in the Kuwaiti population.||URI:||http://hdl.handle.net/123456789/223|
|Appears in Programs:||2050 Molecular Biology|
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