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ACSL4 gen polimorfizminin (rs7886473) metabolik sendrom ve lipid düzeyleri üzerine etkisi

Year 2018, Volume: 43 Number: Supplement 1, 151 - 157, 29.12.2018
https://doi.org/10.17826/cumj.407589

Abstract

Amaç: Lipid metabolizması üzerinden obezite ve metabolik sendromla ilişkisi olabileceğini düşündüğümüz ACSL4 geninin sık görülen rs7886473 A>G polimorfizminin Türk toplumunda metabolik sendrom ve lipid düzeyleri üzerindeki etkisini araştırmayı amaçladık.

Gereç ve Yöntem: Çalışmamıza, Türkiye genelinde takip edilen ve modifiye edilmiş NCEP ATPIII Metabolik Sendrom tanı kriterlerine göre 556 metabolik sendrom olan ve 520 metabolik sendrom olmayan erişkin birey dahil edildi. Metabolik sendrom olan ve olmayan bireylerin ACSL4 gen polimorfizmi Roche Light Cycler 480 Real-Time PCR ile genotiplendi ve karşılaştırıldı.

Bulgular: Metabolik sendrom olan ve metabolik sendrom olmayan bireyler arasında ACSL4 rs7886473 genotip dağılımları arasında anlamlı bir farklılık bulunmadı. Tüm erkeklerin ACSL4 rs7886473 polimorfizmine göre serum total kolesterol, HDL, LDL ve trigliserid düzeyleri karşılaştırıldığında; GG ve AA genotipleri arasında anlamlı bir farklılık bulunmadı. Benzer şekilde tüm kadınlarda da anlamlı farklılık bulunmadı.

Sonuç: Bu çalışma, ACSL4 geni açısından incelemiş olduğumuz rs7886473 gen polimorfizminin metabolik sendrom ve serum lipid düzeyleri üzerine etkisi olmadığını gösterdi. Ancak çalışmamızda incelenmiş olan ACSL4 geninde yaygın görülen yalnızca bir polimorfizmdir. Bu durum ACSL4 geninin lipid metabolizması ve/veya metabolik sendrom üzerine etkili olmadığını değerlendirmek için tek başına yeterli değildir.

References

  • Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.
  • Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-421.
  • Raz I, Eldor R, Cernea S, Shafrir E. Diabetes: Insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage. Diabetes Metab Res Rev 2005;21:3-14.
  • Soupene E, Kuypers FA. Mammalian long-chain acyl-CoA synthetases. Exp Biol Med (Maywood) 2008;233:507-21.
  • Grundy SM, Hypertriglyceridemia, Insulin Resistance, and the Metabolic Syndrome. The American Journal of Cardiology 1999 83;9:25-9.
  • Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002;87:3023-28.
  • Ryysy L, Hakkinen AM, Goto T, Vehkavaara S, Westerbacka J, Halavaara J, et al. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 2000;49:749-58.
  • Adiels M, Taskinen MR, Packard C, Caslake MJ, Soro-Paavonen A, Westerbacka J, et al. Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia 2006;49:755-65.
  • Adiels M, Westerbacka J, Soro-Paavonen A, Hakkinen AM, Vehkavaara S, Caslake MJ, et al. Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance. Diabetologia 2007;50:2356-65.
  • Kotronen A, Westerbacka J, Bergholm R, Pietilainen KH, Yki-Jarvinen H. Liver fat in the metabolic syndrome. J Clin Endocrinol Metab 2007;92:3490-97.
  • Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, et al. Structure and regulation of rat long-chain acyl-CoA synthetase. J Biol Chem 1990;265:8681-85.
  • Lewin TM, Van Horn CG, Krisans SK, Coleman RA. Rat liver acyl-CoA synthetase 4 is a peripheral-membrane protein located in two distinct subcellular organelles, peroxisomes, and mitochondrial-associated membrane. Arch Biochem Biophys 2002;404:263-70.
  • Kim JH, Lewin TM, Coleman RA. Expression and characterization of recombinant rat Acyl-CoA synthetases 1, 4, and 5. Selective inhibition by triacsin C and thiazolidinediones. J Biol Chem 2001;276:24667-73.
  • Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, et al: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005, 112:2735-52.
  • Yan S, Yang XF, Liu HL, Fu N, Ouyang Y, Qing K. Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: an update. World J Gastroenterol 2015;21:3492-98.
  • Jessica ME, Jennifer LF, Lei OL, Rosalind AC. Acyl-coenzyme A synthetases in metabolic control. Curr Opin Lipidol 2010;21:212-17.
  • Mashek DG, Coleman RA. Cellular fatty acid uptake: the contribution of metabolism. Curr Opin Lipidol 2006;17:274-78.
  • Kang MJ, Fujino T, Sasano H, Minekura H, Yabuki N, Nagura H, et al. A novel arachidonate-preferring acyl-CoA synthetase is present in steroidogenic cells of the rat adrenal, ovary, and testis. Proc Natl Acad Sci USA 1997;94:2880-84.
  • Wu X, Li Y, Wang J, Wen X, Marcus MT, Daniels G, et al. Long chain fatty Acyl-CoA synthetase 4 is a biomarker for and mediator of hormone resistance in human breast cancer. PLoS One 2013;8:e77060.
  • Golej DL, Askari B, Kramer F, Barnhart S, Vivekanandan-Giri A, Pennathur S, et al. Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells. J Lipid Res 2011;52:782-93.
  • Cooke M, Orlando U, Maloberti P, Podestá EJ, Cornejo Maciel F. Tyrosine phosphatase SHP2 regulates the expression of acyl- CoA synthetase ACSL4. J Lipid Res 2011;52:1936-48.
  • Mashek DG, Li LO, Coleman RA. Rat long-chain acyl-CoA synthetase mRNA, protein, and activity vary in tissue distribution and in response to diet. J Lipid Res 2006;47:2004-10.
  • Savage DB, Petersen KF, Shulman GI. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 2007;87:507-20.
  • Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 2008;118:829-38.
  • Wymann MP, Schneiter R. Lipid signalling in disease. Nat Rev Mol Cell Biol 2008;9:162-76.
  • Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest 2000;106:171-76.
  • Faergeman NJ, Knudsen J. Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. Biochem J 1997;323:1-12.
  • Thompson AL, Cooney GJ. Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance. Diabetes 2000;49:1761-65.
  • Petrescu AD, Hertz R, Bar-Tana J, Schroeder F, Kier AB. Ligand specificity and conformational dependence of the hepatic nuclear factor-4alpha (HNF-4alpha). J Biol Chem 2002;277:23988-99.
  • Li LO, Ellis JM, Paich HA, Wang S, Gong N, Altshuller G, et al. Liver-specific loss of long chain acyl-CoA synthetase-1 decreases triacylglycerol synthesis and beta-oxidation and alters phospholipid fatty acid composition. J Biol Chem 2009;284:27816-26.
  • Zeman M, Vecka M, Jáchymová M, Jirák R, Tvrzická E, Stanková B, et al. Fatty acid CoA ligase-4 gene polymorphism influences fatty acid metabolism in metabolic syndrome, but not in depression. Tohoku J Exp Med 2009;217:287-93.
  • Kotronen A, Yki-Järvinen H, Aminoff A, Bergholm R, Pietiläinen KH, Westerbacka J, et al. Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts. Eur J Endocrinol 2009;160:593-602.

Effect of ACSL4 gene polymorphism (rs7886473) on metabolic syndrome and lipid levels

Year 2018, Volume: 43 Number: Supplement 1, 151 - 157, 29.12.2018
https://doi.org/10.17826/cumj.407589

Abstract

Purpose: Acyl-CoA synthetase long-chain family member 4 (ACSL4) is thought to be related with obesity and metabolic syndrome via lipid metabolism. We aimed to investigate the effect of the single nucleotide polymorphism (SNP) rs7886473, which is a common intron variant of ACSL4 gene on metabolic syndrome and lipids in Turkish society.

Materials and Methods: Metabolic syndrome (n=556) and non-metabolic syndrome (n=520) patients according to the modified NCEP ATPIII metabolic syndrome criterias were included in the study. SNPs were genotyped with Roche Light Cycler 480 Real-Time PCR and then compared between groups.

Results: There was no significant difference in the genotype frequencies of the ACSL4 gene polymorphism (rs7886473) between the metabolic syndrome and the non-metabolic syndrome patient groups. There were no significant differences in serum total cholesterol, HDL, LDL and triglyceride levels between GG and AA genotypes either in men or women.

Conclusion: This study showed that ACSL4 gene polymorphism (rs7886473) has no effect on metabolic syndrome and serum lipid levels. However, only one common SNP on the ACSL4 gene was examined in our study. In this instance, this study is not enough to determine whether ACSL4 gene is not effective on metabolic syndrome and/or lipid levels. 


References

  • Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.
  • Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-421.
  • Raz I, Eldor R, Cernea S, Shafrir E. Diabetes: Insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage. Diabetes Metab Res Rev 2005;21:3-14.
  • Soupene E, Kuypers FA. Mammalian long-chain acyl-CoA synthetases. Exp Biol Med (Maywood) 2008;233:507-21.
  • Grundy SM, Hypertriglyceridemia, Insulin Resistance, and the Metabolic Syndrome. The American Journal of Cardiology 1999 83;9:25-9.
  • Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002;87:3023-28.
  • Ryysy L, Hakkinen AM, Goto T, Vehkavaara S, Westerbacka J, Halavaara J, et al. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 2000;49:749-58.
  • Adiels M, Taskinen MR, Packard C, Caslake MJ, Soro-Paavonen A, Westerbacka J, et al. Overproduction of large VLDL particles is driven by increased liver fat content in man. Diabetologia 2006;49:755-65.
  • Adiels M, Westerbacka J, Soro-Paavonen A, Hakkinen AM, Vehkavaara S, Caslake MJ, et al. Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance. Diabetologia 2007;50:2356-65.
  • Kotronen A, Westerbacka J, Bergholm R, Pietilainen KH, Yki-Jarvinen H. Liver fat in the metabolic syndrome. J Clin Endocrinol Metab 2007;92:3490-97.
  • Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, et al. Structure and regulation of rat long-chain acyl-CoA synthetase. J Biol Chem 1990;265:8681-85.
  • Lewin TM, Van Horn CG, Krisans SK, Coleman RA. Rat liver acyl-CoA synthetase 4 is a peripheral-membrane protein located in two distinct subcellular organelles, peroxisomes, and mitochondrial-associated membrane. Arch Biochem Biophys 2002;404:263-70.
  • Kim JH, Lewin TM, Coleman RA. Expression and characterization of recombinant rat Acyl-CoA synthetases 1, 4, and 5. Selective inhibition by triacsin C and thiazolidinediones. J Biol Chem 2001;276:24667-73.
  • Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, et al: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005, 112:2735-52.
  • Yan S, Yang XF, Liu HL, Fu N, Ouyang Y, Qing K. Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: an update. World J Gastroenterol 2015;21:3492-98.
  • Jessica ME, Jennifer LF, Lei OL, Rosalind AC. Acyl-coenzyme A synthetases in metabolic control. Curr Opin Lipidol 2010;21:212-17.
  • Mashek DG, Coleman RA. Cellular fatty acid uptake: the contribution of metabolism. Curr Opin Lipidol 2006;17:274-78.
  • Kang MJ, Fujino T, Sasano H, Minekura H, Yabuki N, Nagura H, et al. A novel arachidonate-preferring acyl-CoA synthetase is present in steroidogenic cells of the rat adrenal, ovary, and testis. Proc Natl Acad Sci USA 1997;94:2880-84.
  • Wu X, Li Y, Wang J, Wen X, Marcus MT, Daniels G, et al. Long chain fatty Acyl-CoA synthetase 4 is a biomarker for and mediator of hormone resistance in human breast cancer. PLoS One 2013;8:e77060.
  • Golej DL, Askari B, Kramer F, Barnhart S, Vivekanandan-Giri A, Pennathur S, et al. Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells. J Lipid Res 2011;52:782-93.
  • Cooke M, Orlando U, Maloberti P, Podestá EJ, Cornejo Maciel F. Tyrosine phosphatase SHP2 regulates the expression of acyl- CoA synthetase ACSL4. J Lipid Res 2011;52:1936-48.
  • Mashek DG, Li LO, Coleman RA. Rat long-chain acyl-CoA synthetase mRNA, protein, and activity vary in tissue distribution and in response to diet. J Lipid Res 2006;47:2004-10.
  • Savage DB, Petersen KF, Shulman GI. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev 2007;87:507-20.
  • Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 2008;118:829-38.
  • Wymann MP, Schneiter R. Lipid signalling in disease. Nat Rev Mol Cell Biol 2008;9:162-76.
  • Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest 2000;106:171-76.
  • Faergeman NJ, Knudsen J. Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. Biochem J 1997;323:1-12.
  • Thompson AL, Cooney GJ. Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance. Diabetes 2000;49:1761-65.
  • Petrescu AD, Hertz R, Bar-Tana J, Schroeder F, Kier AB. Ligand specificity and conformational dependence of the hepatic nuclear factor-4alpha (HNF-4alpha). J Biol Chem 2002;277:23988-99.
  • Li LO, Ellis JM, Paich HA, Wang S, Gong N, Altshuller G, et al. Liver-specific loss of long chain acyl-CoA synthetase-1 decreases triacylglycerol synthesis and beta-oxidation and alters phospholipid fatty acid composition. J Biol Chem 2009;284:27816-26.
  • Zeman M, Vecka M, Jáchymová M, Jirák R, Tvrzická E, Stanková B, et al. Fatty acid CoA ligase-4 gene polymorphism influences fatty acid metabolism in metabolic syndrome, but not in depression. Tohoku J Exp Med 2009;217:287-93.
  • Kotronen A, Yki-Järvinen H, Aminoff A, Bergholm R, Pietiläinen KH, Westerbacka J, et al. Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts. Eur J Endocrinol 2009;160:593-602.
There are 32 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research
Authors

Eren Vurgun

İrem Yağmur Diker This is me

Neslihan Çoban

Filiz Geyik This is me

Gamze Güven This is me

Nihan Erginel Ünaltuna

Publication Date December 29, 2018
Acceptance Date July 14, 2018
Published in Issue Year 2018 Volume: 43 Number: Supplement 1

Cite

MLA Vurgun, Eren et al. “ACSL4 Gen Polimorfizminin (rs7886473) Metabolik Sendrom Ve Lipid düzeyleri üzerine Etkisi”. Cukurova Medical Journal, vol. 43, no. Ek 1, 2018, pp. 151-7, doi:10.17826/cumj.407589.