DOI QR코드

DOI QR Code

Serum level of the adiponectin and adiponectin I164T polymorphism in hypertensive adolescents

고혈압 청소년에서의 혈청 adiponectin치와 adiponectin I164T 유전자다형성

  • Lee, Jung Ah (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Gil, Joo Hyun (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Hong, Young Mi (Department of Pediatrics, School of Medicine, Ewha Womans University)
  • 이정아 (이화여자대학교 의과대학 소아과학교실) ;
  • 길주현 (이화여자대학교 의과대학 소아과학교실) ;
  • 홍영미 (이화여자대학교 의과대학 소아과학교실)
  • Received : 2008.05.07
  • Accepted : 2008.10.08
  • Published : 2009.02.15

Abstract

Purpose : Adiponectin is a molecule that plays an important role in the metabolic syndrome. In addition, its concentration is known to be decreased in obesity, type 2 diabetes, and coronary artery disease. Although a relationship between hypertension and serum adiponectin concentrations has been reported by several authors, such findings continue to be debated. We investigated whether hypoadiponectinemia is related to hypertension in adolescents and studied the associated genetic polymorphism. Methods : Forty hypertensive adolescents (Age 16-17 years old) and twenty normotensive matched subjects were included. Serum adipo-nectin, insulin, renin, aldosterone and angiotensin converting enzyme (ACE) levels were compared. Their carotid intima-media thickness (cIMT) and pulse wave velocity (PWV) were measured. Polymorphisms of the adiponectin I164T gene were investigated using polymerase chain reaction (PCR). Results : The hypertensive adolescents had significantly greater cIMT and PWV. In addition, the serum aldosterone, renin and insulin levels were significantly higher in the hypertensive group. The plasma concentrations of adiponectin did not differ significantly between the two groups. TC genotype was not found in our study subjects; they all had the TT genotype of the adiponectine gene. Conclusion : The results of our study showed that adiponectin levels were not significantly different in adolescents with hypertension. There was no distinctive genetic polymorphism observed in this group of patients. Further large scale studies are needed to clarify the association between genetic variations and adiponectin in hypertensive adolescents.

목 적 : Adiponectin은 대사 증후군에서 중요한 역할을 하는 물질이며, 비만, 2형 당뇨, 관동맥 질환 등에서 그 수치가 감소하는 것으로 알려져 있다. 고혈압과 혈청 adiponectin치의 관계는 여러 저자에 의하여 발표되었으나 아직 논란의 여지가 남아있는 상태이다. 우리는 낮은 adiponectin치가 청소년 고혈압과 어떤 관계가 있는지, 또 영향을 끼치는 기전이 유전적인지 혹은 생물학적인 것인지 알고자 유전자 다형성 분석을 하였다. 방 법 : 16에서 17세 사이의 40명의 고혈압 청소년과 20명의 대조군 청소년을 대상으로 각 군의 혈청 adiponectin, insulin, renin, aldosterone, ACE를 측정하여 비교하였다. cIMT와 PWV도 측정하였다. PCR법으로 adiponectin I164T 유전자 다형성을 조사하였다. 결 과 : 고혈압 청소년군에서 cIMT와 PWV가 의미있게 높았다. 혈청 insulin, renin, aldosterone치도 고혈압군에서 의미있게 높았다. 두 군간에 adiponectin치는 의미있는 차이를 보이지 않았다. 본 연구에 참여한 청소년에서는 TC genotype은 발견되지 않았고 모두 TT genotype을 보였다. 결 론 : 결론적으로 adiponectin치는 고혈압 청소년 군에서나 정상군에서나 차이가 없었다. 두 군에서 유전적인 다형성도 보이지 않았다. 더 큰 규모의 연구가 필요할 것으로 생각된다.

Keywords

References

  1. Scherer PE, William S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270:26746-9 https://doi.org/10.1074/jbc.270.45.26746
  2. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matzubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1(adipose most abundant gene transcript 1). Biochem Biophys Res Commun 1996;221:286-9 https://doi.org/10.1006/bbrc.1996.0587
  3. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:10679-703
  4. Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M. Isolation and characterization of GBP28, a novel gelatin- binding protein purified from human plasma. J Biochem 1996;120:803-12 https://doi.org/10.1093/oxfordjournals.jbchem.a021483
  5. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipocyte specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999;257:79-83 https://doi.org/10.1006/bbrc.1999.0255
  6. Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003;46:459-69 https://doi.org/10.1007/s00125-003-1074-z
  7. Kazumi T, Kawaguchi A, Sakai K, Hirano T, Yoshino G. Young men with high normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 2002;25:971-6 https://doi.org/10.2337/diacare.25.6.971
  8. Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 2002;87:2764-9 https://doi.org/10.1210/jc.87.6.2764
  9. Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet 2003;361:226-8 https://doi.org/10.1016/S0140-6736(03)12255-6
  10. Linsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002; 360: 57-8 https://doi.org/10.1016/S0140-6736(02)09335-2
  11. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Novel modulator for endothelial adhesion molecules: Adipocyte-derived plasma protein adiponectin. Circulation 1999;100:2473-6
  12. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP- dependent pathway. Circulation 2000;102:1296-301
  13. Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, et al. Adipocyte-derived plasma protein adiponectin acts as a platelet derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation 2002;105:2893-8 https://doi.org/10.1161/01.CIR.0000018622.84402.FF
  14. Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 2000;32:47-50 https://doi.org/10.1055/s-2007-978586
  15. Furuhashi M, Ura N, Higashiura K, Murakami H, Tanaka M, Moniwa N, et al. Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. Hypertension 2003;42:76-81 https://doi.org/10.1161/01.HYP.0000078490.59735.6E
  16. Ohashi K, Ouchi N, Kihara S, Funahashi T, Nakamura T, Sumitsuji S, et al. Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease. J Am Coll Cardiol 2004;43:1195-200 https://doi.org/10.1016/j.jacc.2003.10.049
  17. Hulver MW, Saleh O, MacDonald KG, Pories WJ, Barakat HA. Ethnic differences in adiponectin levels. Metabolism 2004;53:1-3 https://doi.org/10.1016/j.metabol.2003.07.002
  18. Kondo H, Shimomura I, Matzuzawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes 2002;51:2325-8 https://doi.org/10.2337/diabetes.51.7.2325
  19. Ogden CL, Flegal KM, Caroll MD, Johnson CL. Prevalence and trends in overweight among US children and adolescent, 1999-2000 JAMA 2002;288:1728-32 https://doi.org/10.1001/jama.288.14.1728
  20. Francischetti EA, Genelhu VA. Obesity-hypertension: an ongoing pandemic. Int J Clin Pract 2007;61:269-80 https://doi.org/10.1111/j.1742-1241.2006.01262.x
  21. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, et al. Plasma concentrations of novel, adipose- specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000;20:1595-9
  22. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, et al. Weight reduction increases plasma levels of an adipose-derived, anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001;86:3815-9 https://doi.org/10.1210/jc.86.8.3815
  23. Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003;23:85-9 https://doi.org/10.1161/01.ATV.0000048856.22331.50
  24. Yamamoto Y, Hiroshi H, Saito I, Tomita M, Taniyama M, Matsubara K, et al. Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japaneses population. Clin Sci 2002;103: 137-42 https://doi.org/10.1042/CS20010336
  25. Adamczak M, Wiecek A, Funahashi T, Chudek J, Kokot F, Matsuzawa Y. Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens 2003;16:72-5 https://doi.org/10.1016/S0895-7061(02)03197-7
  26. Obes ResYang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res 2002;10:1104-10 https://doi.org/10.1038/oby.2002.150
  27. Mallamaci F, Zoccali C, Cuzzola F, Tripepi G, Cutrupi S, Parlongo S, et al. Adiponectin in essential hypertension. J Nephrology 2002;15:507-11
  28. Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes 2002;51:2325-8 https://doi.org/10.2337/diabetes.51.7.2325
  29. Ohashi K, Ouchi N, Kihara S, Funahashi T, Nakamura T, Sumitsuji S, et al. Adiponectin I164T mutation is associated with the metabolic syndrome. J Am Coll Cardiol 2004;43: 1195-200 https://doi.org/10.1016/j.jacc.2003.10.049
  30. Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S, et al. Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the AMP1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 2002;11:2607-14 https://doi.org/10.1093/hmg/11.21.2607