Association hindiii polymorphism LPL with the formation of lipid profile serum
Abstract
Перенести в английский вариант
Background and aims: we have analyzed the frequencies of HindIII polymorphism of lipoprotein lipase gene (LPL) and lipid profile in Caucasian population of West Siberia and the groups this high and low total cholesterol (TC) level.
Material and methods: The patients included in the analyses were selected based on TC level from population sample surveyed in frame of HAPIEE project (9360 participants, aged 45–69, men 50 %). Totally 259 patients with highest TC level (>300 mg/dl) and 228 patients with lowest TC level (< 200 mg/dl) and 170 randomly selected patients (mean TC level – 235.8 ± 43.9 mg/dl) were included. The differences of TC level between groups are significant. The plasma lipid levels were determined by standard enzymatic assays. The subfractional profile of LDL was determined by method of electrophoresis. The HindIII polymorphism (22125T/G) of LPL gene was analyzed by RELF-PCR.
Results: Frequencies of H+H+, H+H- and H-H- genotypes were 61 %, 35 % and 4 % in population. The frequency of H- allele was 0.22, 0.28 and 0.29 in HAPIEE population, low and highest TC level groups, respectively (p > 0.05). We have found the association of HindIII polymorphism of LPL gene with TG level in HAPIEE population (p = 0.002). We have found the association of polymorphism HindIII of gene LPL with minor peak on a descending curve of the subfractional profile LDL (p = 0.02). Depression of activity LPL leads to depression of formation of the fine dense particles rich of cholesterol and the maintenance of the particles rich of triglyceride that can lead to development combined hyperlipidemia.
Conclusions: The Caucasian population of West Siberia is not significantly differs from populations of Europe by frequencies of alleles and genotypes. The genotype H+H+ of HindIII polymorphism of LPL gene has been associated with high TG level. The polymorphism HindIII of gene LPL has been associated with the subfractional profile LDL.
About the Authors
E. V. ShakhtshneiderRussian Federation
SB RAMS
Research Institute of Internal and Preventive Medicine
630089
Boris Bogatkov str., 175/1
Novosibirsk
Yu. I. Ragino
Russian Federation
SB RAMS
Research Institute of Internal and Preventive Medicine
630089
Boris Bogatkov str., 175/1
Novosibirsk
Ya. V. Polonskaya
Russian Federation
SB RAMS
Research Institute of Internal and Preventive Medicine
630089
Boris Bogatkov str., 175/1
Novosibirsk
E. V. Kashtanova
Russian Federation
SB RAMS
Research Institute of Internal and Preventive Medicine
630089
Boris Bogatkov str., 175/1
Novosibirsk
M. I. Voevoda
Russian Federation
SB RAMS
Research Institute of Internal and Preventive Medicine
630089
Boris Bogatkov str., 175/1
Novosibirsk
References
1. Hoffmann M. M., Jacob S., Luft D., Schmülling R. M., Rett K., März W., Häring H. U., Matthaei S. Type I hyperlipoproteinemia due to a novel loss of function mutation of lipoprotein lipase, Cys (239)-->Trp,associated with recurrent severe pancreatitis // J. Clin. Endocrin. Metab. 2000. 85 (12). P. 4795–4798.
2. Merkel M., Eckel R., Goldberg i. Lipoprotein lipase: genetics, lipid uptake, and regulation // J. Lipid Res. 2002. Vol. 43. P. 1997–2006.
3. Monsalve M. V., Henderson H., Roederer G., Julien P., Deeb S., Kastelein J. J. P., Peritz L., Devlin R., Bruin T., Murthy M. R. V., Gagne C., Davignon J., Lupien P. J., Brunzell J. D., Hayden M. R. A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries // J. Clin. Invest. 1990. Vol. 86. P. 728–734.
4. Brunzell J. D., Deeb S. S. Familial lipoprotein lipase deficiency, apo CII deficiency and hepatic lipase deficiency // In: Scriver C. R., Beaudet A. L., Sly W. S., Valle D., eds. The Metabolic and Molecular Bases of Inherited Disease. 8 ed. N. Y: McGraw-Hill, 2001. P. 2789–2816.
5. Deeb S. S. Association of variants in lipase genes with lipid levels and coronary artery disease // In: Scriver C. R., Beaudet A. L., Sly W. S., Valle D., Vogelstein B. eds. The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). N. Y.: McGraw-Hill, 2013. Chap 117 S.
6. Jaap Rip, Melchior C. Nierman, Colin J. Ross, Jan WouterJukema, Michael R. Hayden, John J. P. Kastelein, Erik S. G. Stroes, Jan Albert. Kuiven hoven Lipoprotein Lipase S447X aNaturally Occurring Gain-of-Function Mutation // Arterioscler. Thromb. Vasc. Biol. 2006. Vol. 26. P. 1236–1245.
7. Lopez-Miranda J., Cruz G., Gomez P., Marin C., Paz E., Perez-Martinez P., Fuentes F. J., Ordovas J. M., Perez-Jimenez F. The influence of lipoprotein lipase gene variation on postprandial lipoprotein metabolism. // J. Clin. Endocr. Metab. 2004. Vol. 89. Р. 4721–4728.
8. Austin M. A., King M., Vranizan K. M., Krauss R. M. Atherogenic lipoprotein phenotype A proposed genetic marker for coronary heart disease risk // Circulation. 1990. Vol. 82. P. 495–506.
9. Chapman M. J., Guerin M., Bruckert E. Atherogenic, dense LDL pathophysiology and new therapeutic approaches // Eur. Heart J. 1998. Vol. 19. P. 24–30.
10. Chapman M. J., Bruckert E. The atherogenic role of triglycerides and small, dense low density lipoproteins: impact of ciprofibrate therapy // Atherosclerosis. 1996 Jul. Vol. 124. Suppl: P. 21–28.
11. Havel R. J. Lipid transport function of lipoproteins in blood plasma // Am. J. Phys. 1987. Jul. Vol. 253 (1 Pt 1). P. E1–E5.
12. Fisher R. M., Coppack S. W., Humphreys S. M., Gibbons G. F., Frayn K. N. Human triacylglycerol-rich lipoprotein subfractions as substrates for lipoprotein lipase // Clin. Chim. Acta. 1995. Apr. Vol. 236 (1). P. 7–17.
13. Chasman D. I., Paré G., Mora S., Hopewell J. C., Peloso G., Clarke R., Cupples L. A., Hamsten A., Kathiresan S., Mälarstig A., Ordovas J. M., Ripatti S., Parker A. N., Miletich J. P., Ridker P. M. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis // PLoS Genet. 2009. Nov. Vol. 5 (11). P. e1000730.
14. Шахтшнейдер Е. В. Полиморфизм гена аполипопротеина Е у мужчин с коронарным атеросклерозом в Сибири / Е. В. Шахтшнейдер [и др.] // Бюл. эксперим. биологии и медицины. – 2010. – Т. 150, № 9. – С. 324–327.
15. Рагино Ю. И. Комплекс липидных и нелипидных биомаркеров, ассоциированных с ИБС, в мужской Сибирской популяции Ю. И. Рагино [и др.] // Кардиоваскулярная терапия и профилактика (прил.): мат. Рос. нац. конгресса кардиологов. – Москва, 2009. – № 8 (6). – С. 297–298.
16. Shakhtsneider E. V., Allakhverdyan A. A., Kulikov I. V., Maksimov V. N., Romashchenko A. G., Nikitin Yu. P., Malyutina S. K., Voevoda M. I. The influence of genes on lipid metabolism in West Siberia caucasian population // Аtherosclerosis. 2010. Suppl. 11. N 2, 78th European Atherosclerosis Society Congress – Hamburg. Germany. P. 117.
Review
For citations:
Shakhtshneider E.V., Ragino Yu.I., Polonskaya Ya.V., Kashtanova E.V., Voevoda M.I. Association hindiii polymorphism LPL with the formation of lipid profile serum. Ateroscleroz. 2014;10(2):24-30. (In Russ.)