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analysis of 9 exonic synonymous polymorphisms (23 subjects) revealed a common haplotype shared by carrier families of the same pair of mutations. Therefore, recurrent recombination events were ruled out as a mechanism for these unfortuitous associations. Interestingly, two pairs were already reported in other European countries. Mutations K290R/C292W were found in Belgium and mutations E256K/I402T in Sweden. This suggests that an ancient mutagenic event (recombination or double hit) gave rise to a single allele bearing two defective mutations in common European ancestors. These findings underscore that allelic heterogeneity might reflect the natural mutagenic potential of the LDL receptor gene. ~ - ~ S I X LIPOPROTEIN LIPASE SNPS, LEVELS OF TRIGLYCERIDE AND HDL, AND RISK OF ISCHEMIC HEART DISEASE (IHD); THE COPENHAGEN CITY HEART STUDY H.H. Wittrup 1, R.V. Andersen 1, G. Jensen2, R. Steffensen3, A. Tybjaerg-Hansen2'4, B.G. Nordestgaard 1.2. ]Department of Clinical
Biochemistry, Herlev University Hospital, Copenhagen," 2The Copenhagen City Heart Study, Bispebjerg University Hospital, Copenhagen," 3Department of Medicine B, Hilleroed Hospital, Hilleroed; 4Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark We genotyped 4946 women and 3997 men from the general population and 242 female and 679 male IItD patients for six lipoprotein lipase SNPs: two promoter SNPs, T(-93)G and G(-53)C, and four coding region SNPs, Asp9Asn, Gly188Glu, Asn291Ser and Ser447Ter. In the general population, 74% were wild type(N/N), 16.8% 447/N, 4.2% 291/N, 2.5% -93,9/N, 1.1% 447/447, and 0.1% were 188/N, while 1.4% were distributed on 10 other genotypes. Plasma triglyceride levels in women were, compared with N/N women(1.69 mmol/L), altered by +64%(188/N), +14%(291/N), +4%(-93,9/N), -7%(447/N) and -11%(447/447); equivalent values in men(N/N: 2.05 mmol/L) were +38%, -1%, +20%, -10% and -22%. Furthermore, ItDL cholesterol levels in women was altered, compared with N/N women(1.72 mmol/L), by -25%(188/N), -10%(291/N), -4%(-93,9/N), +4%(447/N) and +1%(447/447); equivalent values in men(N/N: 1.38mmol/L) were -31%, -6%, -4%, +4% and +12%. These results were similar after stratification for apoE genotype. Compared with N/N, odds ratio for IItD was 4.7(95%CI: 1.120) for 188/N, 1.0(0.8 1.3) for 291/N, 1.6(1.22.1) for 9/N, 1.0(0.9 1.2) for 447/N and 1.1(0.7 1.8) for 447/447. Finally, in a prospective study of 23 years follow-up, relative risk of IItD compared with N/N was 1.0(0.7 1.4) for 291-carriers, 1.7(1.2 2.4) for 9-carriers and 1.1(1.0 1.4) for 447-carriers. Results on IItD risk were similar after stratification for sex and apoE genotype. In conclusion, genetic variability in lipoprotein lipase can explain up to 70% difference in plasma triglycerides, up to 40% difference in ItDL cholesterol, and up to 5-fold difference in risk of IItD. ~-~
RELATIONSHIP BETWEEN TOTAL ANTIOXIDANT STATUS AND BLOOD LIPIDS IN HEALTHY WOMEN
M. Andonovska. Medical Center, Kumanovo, Republic of Macedonia Several studies have shown only small linear correlation between the total antioxidants and different blood analytes. The aim of our study was to investigate the type of interrelationships between the Total Antioxidant Status (TAS) assay that is used to monitor the overall functioning of the antioxidant defense system, and blood lipids. TAS, total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglycerides (TG) were determined in 87 apparently healthy women. Information was collected with a self-administrated validate questionnaire. All women were nonsmokers, never received hormone replacement therapy, they used no vitamins, had no hypertension or any other disease. TAS was determined using Randox commercial kit. TC and TG were measured enzimatically, HDL-C via precipitation method and LDL-C was estimated using Friedewald equation. In order to discern trends in data nonlinear regression analyze was used and the following polynomial equations were obtained: y--0.0134x2 + 0.1001x +1.0372, (r--0.47) for the relationship between TAS and TC and y--0.01x2 +0.0302 + 1.2055 (r--0.44) for the relationship between TAS and HDL-C. The correlation between TAS and other lipids was very pour. These results suggest that predicted TAS is negatively interacted by TC and the most atherogenic lipid, LDL-C, in a polynomial fashion. The obtained correlation suggest that increased intake of antioxidants could have a role in preventing coronary heart disease.
~ - - ~ DOES IMMUNOMODULATION OF CORONARY ATHEROSCLEROSIS HAVE THE FUTURE? E. Andreeva. St. Petersburg State Medical Academy, St. Petersburg, Russia Shifts of immunologic system are revealed in patients with atherosclerosis and subsequently in patients with ischemic heart disease. It was investigated if medicine contained polyunsaturated fatty acids affected on immunologic system in patients suffered from ischemic heart disease (IHD). Methods: Sixty one patients with ischemic heart disease were examined. Patients were divided into two groups. Patients of first control group were treated with aspirin, beta-blockers and nitrates. Patients of second group administered aspirin, beta-blockers, nitrates and pills contained polyunsaturated fatty acids. Blood samples were taken before treatment and three weeks after the start of treatment. We studied level of tumor necrosis factor alpha, circulating immune complexes (CIC) and level of immunoglobulin (IG) A, G and M. Results: Immunologic shifts were revealed in patients before treatment: sixty eight percent of patients had an increased level of TNF-ct, increased level of IG A and IGG were observed in fifty percent and thirty eight percent of patients correspondingly, increased level of CIC were found in twenty three percent of patients. Three weeks after treatment there was no significant changes in immune profile of control group patients, in patients of studying group we observed decreasing of TNF-ct and CIC level on thirty nine percent and sixteen percent correspondingly. Conclusion: Alterations in immune system in patients with IHD have been found. Administration of polyunsaturated fatty acids in treatment of patients with IHD improves immunologic shifts in patients with IHD. The future of coronary atherosclerosis treatment is the individual complex correction of immune system shifts. ~-~
LOCAL LIPID DEPOSITION IN UNINVOLVED HUMAN AORTIC INTIMA CORRELATES W I T H INFLAMMATORY CELLS' ACCUMULATION AND INFLAMMATORY ACTIVATION OF VESSEL WALL CELLS
E.R. Andreeva 1, I.A. Mikhailova 1, A.N. Orekhov2. ]Institute of Experimental Cardiology, Cardiocenter, 2Institute for Atherosclerosis Research, Russian Academy of Natural Science, Moscow, Russia The presence of inflammatory cells and different cyto- and chemokines in atherosclerotic lesions in human arteries gave the reason to consider inflammatory reaction as an essential component of atherosclerotic lesions. However, the mechanisms initiating inflammatory reaction, probably, even before occurence of visible lesions, remain still unclear. Local lipid accumulation can be assumed as one of the initiators of an inflammatory reaction. We examined, whether there is a correlation between lipid accumulation in the normal intima and initial manifestations of inflammatory rection: inflammatory cells infiltration and inflammatory activation of cells in the intima. In grossly normal intima (DIT) lipids were revealed with Oil Red O (ORO). Lymphocytes and macrophages have been immunocytochemically identified in the sites with different intensity of ORO staining. Inflammatory cells' activation have been characterized with the expression of HLA-DR antigen expression. We have found, that local lipid accumulation in DIT significantly correlates with increase of inflammatory cells' number (r-0.59, p<0.001) and increase of HLA-DR antigen expression (r-0.80, p<0.001). Thus, we have demonstrated the significant correlation between local lipid accumulation in DIT and initial phases of inflammatory reaction: local increase of inflammatory cells' number and inflammatory activation of the vessel wall cells. ~
APOLIPOPROTEIN E POLYMORPHISM AND CAROTID ATHEROSCLEROSIS IN PATIENTS W I T H CORONARY DISEASE
C. Fernandez-Miranda, J.L. Aranda, M.A. Martin, J. Arenas, V. Nunez, A. Gomez De La Camara. Hospital Universitario 12 De Octubre, Madrid,
Spain Background: Apolipoprotein (apo) E polymorphism plays a role in the development of coronary disease, but their involvement in carotid atherosclerosis is controversial. The aim of this study was to evaluate the role of apo E polymorphism in the development of subclinical carotid atherosclerosis in patients with coronary disease. Methods: In 226 consecutive patients (192 men and 34 women; age: 60.9[7.8] years) with coronary disease, apo E genotypes were performed
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