Impact of 75G/A apolipoprotein AI gene polymorphism on lipid profile in obese and non-obese men

• Autorzy: Wlodarczyk M. , Wrzosek M. , Nowicka G.

Warianty tytułu

PL

Związek polimorfizmu 75G/A w genie apolipoproteiny AI z poziomem lipidów u otyłych i nie otyłych mężczyzn

• Języki publikacji: EN

Abstrakty

EN

Introduction: Obesity is a multifactorial disorder leading to disturbances in lipid metabolism and adverse plasma lipid profiles. 75G/A polymorphism in the apolipoprotein AI (apo AI) gene promoter has been shown to affect plasma HDL-cholesterol and apolipoprotein AI concentrations. However, the impact of this genetic variant on lipid profiles in obese subjects has not been well recognized. In the present study the relationship between 75G/A apo AI gene polymorphism (rs 670) and plasma lipids and apo AI concentrations in obese and non-obese males was assessed. Material and Methods: 114 men who were not taking lipid lowering drugs were examined: control group with body mass index (BMI) less than 25 (n = 34), overweight with BMI ranged 25-29 (n = 51) and obese subjects with BMI > 30 (n - 29). The 75G/A gene polymorphism of apo AI was determined by PCR-based method. Results: Higher serum HDL-cholesterol and apo AI concentrations in A allele carriers compared to GG homozygotes were observed in men with proper body mass (p = 0.037 and p = 0.056, respectively) and in overweight subjects (p = 0.0072 and p = 0.018, respectively) but not in obese men. Therefore, interaction may be suggested between 75G/A genetic variants in apo AI gene with obesity and its influence on plasma HDL-cholesterol and apo AI concentrations.

PL

Wstęp: Otyłość jest wieloczynnikową chorobą prowadzącą do zaburzeń metabolizmu lipidów. Dotychczasowe dane sugerują, że polimorfizm 75G/A w promotorze genu apolipoproteiny Al wpływa na stężenie różnych frakcji lipoprotein w surowicy. Jednakże znaczenie tego polimorfizmu w odniesieniu do profilu lipidowego u osób otyłych nie zostało udokumentowane. Cel: Celem niniejszej pracy było określenie związku pomiędzy polimorfizmem 75G/A genu apo Al (rs670) a stężeniem lipidów i apolipoproteiny Al u otyłych i nie otyłych mężczyzn. Materiały i metody: Polimorfizm 75G/A genu apo Al oznaczono u 114 mężczyzn nie stosujących terapii obniżającej stężenie lipidów, spośród których 26 było otyłych (BMI > 30), 49 z nadwagą (BMI 25-29), zaś 39 mężczyzn miało prawidłową masą ciała (BMI < 25). Wyniki: W grupie osób z prawidłową masą ciała oraz z nadwagą, będących nosicielami allela A stwierdzono wyższe stężenie HDL-cholesterolu (p = 0,013) i apolipoproteiny Al (p = 0,009) w stosunku do homozygot GG. Natomiast mężczyźni otyli z allelem A polimorfizmu 75G/A genu apo Al w porównaniu do tych z genotypem GG charakteryzowali się wyższym poziomem cholesterolu całkowitego (p = 0,011) i LDL-cholesterolu (p = 0,003). Wnioski: Uzyskane wyniki sugerują, że badany polimorfizm 75G/A genu apo Al wpływa na stężenie HDL-cholesterolu i apolipoproteiny Al w surowicy osób z BMI < 30, zaś otyłość zmienia tę relację i u osób z BMI > 30 polimorfizm 75G/A apo Al sprzyja wyższym stężeniom cholesterolu całkowitego i LDL-cholesterolu.

Słowa kluczowe

EN

man; cholesterol; HDL-cholesterol; apolipoprotein; body mass index; obesity; gene polymorphism; lipid profile

• Wydawca: -
• Czasopismo: Żywienie Człowieka i Metabolizm
• Rocznik: 2014
• Tom: 41
• Numer: 2
• Opis fizyczny: p.69-77,ref.

Twórcy

autor

Wlodarczyk M.

• Department of Nutrigenomics, National Food and Nutrition Institute in Warsaw, Powsinska 61/63, 02-903 Warsaw, Poland
• Department of Pharmacogenomics, Medical University of Warsaw, Warsaw, Poland

autor

Wrzosek M.

• Department of Pharmacogenomics, Medical University of Warsaw, Warsaw, Poland

autor

Nowicka G.

• Department of Pharmacogenomics, Medical University of Warsaw, Warsaw, Poland

Bibliografia

• 1. Mooradian A.D., Haas M.J., Wehmeier K.R., Wong N.C.: Obesity-related changes in high-density lipoprotein metabolism. Obesity (Silver Spring), 2008, 16, 1152- 60
• 2. Gotto A.M., Brinton E.A.: Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report and update. J. Am. Coll. Cardiol., 2004, 43, 717-24
• 3. Rohrer L„ Hersberger M„ von Eckardstein A.: High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease. Curr. Opin. Lipidol., 2004, 15, 269-278
• 4. Gordon D.J., Probstfield J.L., Garrison R.J.: High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation, 1989, 79, 8-15.
• 5. Rashid S., Genest J.: Effect of obesity on high-density lipoprotein metabolism. Obesity (Silver Spring), 2007, 15, 2875-88.
• 6. Vajo Z„ Terry J.G., Brin- ton E.A.: Increased intra-abdominal fat may lower HDL levels by increasing the fractional catabolic rate of Lp A-I in postmenopausal women. Atherosclerosis, 2002, 160, 495-501
• 7. Smith J.D.: Dysfunctional HDL as a diagnostic and therapeutic target. Arterioscler. Thromb. Vase. Biol., 2009, 30, 151-155.
• 8. Weissglas-Volkov D., Pajukanta P.: Genetic causes of high and low serum HDL-cholesterol. J. Lipid. Res., 2010, 51, 2032-57.
• 9. Ordovas J.M.: The quest for cardiovascular health in the genomic era: nutrigenetics and plasma lipoproteins. Proc. Nutr. Soc., 2004, 63, 145-52-
• 10. Li Y., Yin R., Zhou Y., et al.: Associations of the apolipoprotein A-I gene polymorphism and serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations. Int. J. Mol. Med., 2008, 21, 753-64
• 11. Albahrani A.I., Usher J.J., Alkindi M., et al.: Apolipoprotein Al-75 G/A (Ml-) polymorphism and lipoprotein(a); anti- vs. pro-Atherogenic properties. Lipids Health Dis., 2007, 6, 19
• 12. Reguero J.R., Cubero G.I., Batalla A., et al..: Apolipoprotein Al gene polymorphisms and risk of early coronary disease. Cardiology, 1998, 90, 231-5.
• 13. Jeenah M., Kessling A., Miller N., Humphries S.E.: G to A substitution in the promoter region of the apolipoprotein A gene is associated with elevated serum apolipoprotein Al and high density lipoprotein cholesterol concentrations. Mol. Biol. Med., 1990, 7, 233-41.
• 14. Talmud P.J., Ye S., Humphries S.E.: Polymorphism in the promoter region of the apolipoprotein Al gene associated with differences in apolipoprotein Al levels: the European Atherosclerosis Research Study. Genet. Epidemiol., 1994, 11, 265-80
• 15. Marasco O., Melina F., Mele E.: Linkage disequilibrium of three polymorphic RFLP markers in the apolipoprotein AI-CIII gene cluster on chromosome 11. Hum. Genet., 1993, 91, 169-74
• 16. Juo S.H., Wyszynski D.F., Beaty T.H., et al.: Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: a meta-analysis. Am. J. Med. Genet., 1999, 82, 235-41.
• 17. Ordovas J.M., Corella D., Cupples L.A.: Polyunsaturated fatty acids modulate the effects of the APOAl G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study. Am. J. Clin. Nutr., 2002, 75, 38-46.
• 18. Minnich A., DeLangavant G., Lavigne J., et al..: G->A substitution at position - 75 of the apolipoprotein A-I gene promoter. Evidence against a direct effect on HDL cholesterol levels. Arterioscler. Thromb. Vase. Biol., 1995, 15, 1740-5.
• 19. James W.P: The epidemiology of obesity: the size of the problem. J. Intern. Med., 2008, 263, 336-352 -
• 20. Pulkkinen A., Viitanen L., Kare- inen A., et al.: Mspl polymorphism at +83 bp in intron 1 of the human apolipoprote­in Al gene is associated with elevated levels of HDL cholesterol and apolipoprotein Al in nondiabetic subjects but not in type 2 diabetic patients with coronary heart disease. Diabetes Care, 2000, 23, 791-5
• 21. Garrison R.J., Wilson P.W., Castelli W.P., et al.: Obesity and lipoprotein cholesterol in the Framingham offspring study. Metabolism, 1980, 29, 1053-60.
• 22. Lamon-Fava S., Wilson P.W., Schaefer E.J.: Impact of body mass index on coronary heart disease risk factors in men and women. The Framingham Offspring Study. Arterioscler. Thromb. Vase. Biol., 1996, 16, 1509-15.
• 23. Schaefer E.J., Lamon-Fa- va S., Ordovas J.M., et al.: Factors associated with low and elevated plasma high density lipoprotein cholesterol and apolipoprotein A-I levels in the Framingham Offspring Study. J. Lipid. Res., 1994, 35, 871-82.
• 24. Ruan X., Li Z., Zhang Y„ et al: Apolipoprotein A-I possesses an anti-obesity effect associated with increase of energy expenditure and up-regulation of UCPl in brown fat. J. Cell. Mol. Med., 2011, 15, 763-72-
• 25. Smith J.D., Brinton E.A., Breslow J.L.: Polymorphism in the human apolipoprotein A-I gene promoter region. Association of the minor allele with decreased production rate in vivo and promoter activity in vitro. J. Clin. Invest., 1992, 89, 1796-800.
• 26. Tuteja R., Tuteja N., Melo C., et al.: Transcription efficiency of human apolipoprotein A-I promoter varies with naturally occurring A to G transition. FEBS Lett., 1992, 304, 98-101.-
• 27. Larson I.A., Ordovas J.M., Barnard J.R., et al.: Effects of apolipoprotein A-I genetic variations on plasma apolipoprotein, serum lipoprotein and glucose levels. Clin. Genet., 2002, 61, 176-84.
• 28. Chen E.S., Mazzot- ti D.R., Furuya T.K., et al.: Apolipoprotein Al gene polymorphisms as risk factors for hypertension and obesity. Clin. Exp. Med., 2009, 9, 319-25.
• 29. Do H.Q., Nazih H., Luc G.: Influence of cholesteryl ester transfer protein, peroxisome proliferator- -activated receptor alpha, apolipoprotein E, and apolipoprotein A-I polymorphisms on high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I:A-II concentrations: the Prospective Epidemiological Study of Myocardial Infarction study. Metabolism, 2009, 58 283-9
• 30. Buzza M., Fripp Y„ Mitchell R.J.: Apolipoprotein AI and CIII gene polymorphisms and their association with lipid levels in Italian, Greek and Anglo-Irish populations of Australia. Ann. Hum. Biol., 2001, 28, 481-90.
• 31. Phillips C.M., Goumidi L., Bertrais S.: Gene-nutrient interactions and gender may modulate the association between ApoAl and ApoB gene polymorphisms and metabolic syndrome risk. Atherosclerosis, 2011, 214, 408-14
• 32. Lopez-Miranda J., Ordovas J.M., Espino A.: Influence of mutation in human apolipoprotein A-l gene promoter on plasma LDL cholesterol response to dietary fat. Lancet, 1994, 21, 343: 1246-9
• 33. Mata P., Lopez-Miranda J., Pocovi M.: Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation. Atherosclerosis, 1998, 137, 367-76.
• 34. Lamina C., Forer L., Schonherr S., et al.: Evaluation of gene-obesity interaction effects on cholesterol levels: A genetic predisposition score on HDL-cholesterol is modified by obesity. Atherosclerosis, 2012, 225, 363-369
• 35. Yin R.X., Wu D.F., Miao L„ et al.: Several genetic polymorphisms interact with overweight/obesity to influence serum lipid levels. Cardiovascular Diabetology, 2012, 11, 123.
• 36. Yamada Y., Kato K., Kameyama T., et al.: Genetic factors for obesity. Int. J. Mol. Med., 2006, 18, 843-51.
• 37. Luptáková L., Siváková D., Cvicelová M., et al.: Power of biomarkers and their relative contributions to metabolic syndrome in Slovak adult women. Ann. Hum. Biol., 2013, 40, 132-8.