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Angiotensin-converting enzyme gene insertion/deletion polymorphism is not associated with BMI in Korean adults

  • Kwon, Insu (Research Institute of Sports Science & Industry, Hanyang University)
  • Received : 2020.03.16
  • Accepted : 2020.03.28
  • Published : 2020.03.31

Abstract

[Purpose] Recent studies have demonstrated a probable association between ACE I/D polymorphism and obesity. Thus, this study aimed to investigate whether ACE I/D polymorphism influenced the susceptibly of developing obesity in Korean adults. [Methods] A total of 353 healthy Korean adults aged between 30 and 82 years were recruited, including 157 males and 196 females. Among the participants, 103 (29.2 %) were classified as normal (BMI < 23 kg/m2), 117 (33.1 %) as overweight (23 kg/m2 ≤ BMI < 25 kg/m2), and 133 (37.7 %) as obese (BMI ≥ 25 kg/m2). ACE polymorphism (rs1799752) analysis was performed using the MGB TaqMan® SNP Genotyping assay with 3 types of primers and 2 types of probes. The distributions of the ACE genotypes and allele frequencies were analyzed among the three groups using the Hardy-Weinberg equilibrium, chi-square tests, and multiple regression analysis. [Results] The distribution of the ACE genotypes were as follows: normal [II: n=38 (36.9 %), ID: n=46 (36.8 %), DD: n=19 (18.4 %)], overweight [II: n=43 (36.8 %), ID: n=55 (47.0 %), DD: n=19 (16.2 %)], and obese [II: n=41 (30.8 %), ID: n=76 (57.0 %), DD: n=16 (12.0 %)]. Unexpectedly, the I allele, rather than the D allele, was common in the obese group. [Conclusion] ACE I/D polymorphism is not associated with BMI in Korean adults. Thus, it is unlikely to be a powerful candidate gene for obesity in Korean adults.

Keywords

Acknowledgement

The author declares that there is no conflict of interest regarding the publication of this article.

References

  1. Apovian CM, Riffenburg KM. Perspectives on the global obesity epidemic. Curr Opin Endocrinol Diabetes Obes. 2017;24:307-9. https://doi.org/10.1097/MED.0000000000000362
  2. Engin A. The Definition and Prevalence of Obesity and Metabolic Syndrome. Adv Exp Med Biol. 2017;960:1-17. https://doi.org/10.1007/978-3-319-48382-5_1
  3. Gregg EW, Shaw JE. Global Health Effects of Overweight and Obesity. N Engl J Med. 2017;377:80-1. https://doi.org/10.1056/NEJMe1706095
  4. Ergoren MC, Soyler G, Sah H, Becer E. Investigation of potential genomic biomarkers for obesity and personalized medicine. Int J Biol Macromol. 2019;122:493-8. https://doi.org/10.1016/j.ijbiomac.2018.10.059
  5. Yoo KH, Yim HE, Bae ES, Hong YS. Genetic Contributions to Childhood Obesity: Association of Candidate Gene Polymorphisms and Overweight/Obesity in Korean Preschool Children. J Korean Med Sci. 2017;32:1997-2004. https://doi.org/10.3346/jkms.2017.32.12.1997
  6. Sinha R, Jastreboff AM. Stress as a common risk factor for obesity and addiction. Biol Psychiatry. 2013;73:827-35. https://doi.org/10.1016/j.biopsych.2013.01.032
  7. Raynor HA, Champagne CM. Position of the Academy of Nutrition and Dietetics: Interventions for the Treatment of Overweight and Obesity in Adults. J Acad Nutr Diet. 2016;116:129-47. https://doi.org/10.1016/j.jand.2015.10.031
  8. Mao S, Huang S. A meta-analysis of the association between angiotensin-converting enzyme insertion/ deletion gene polymorphism and the risk of overweight/obesity. J Renin Angiotensin Aldosterone Syst. 2015;16:687-94. https://doi.org/10.1177/1470320313501218
  9. Fyhrquist F, Saijonmaa O. Renin-angiotensin system revisited. J Intern Med. 2008;264:224-36. https://doi.org/10.1111/j.1365-2796.2008.01981.x
  10. Kumar R, Singh VP, Baker KM. The intracellular renin-angiotensin system: a new paradigm. Trends Endocrinol Metab. 2007;18:208-14. https://doi.org/10.1016/j.tem.2007.05.001
  11. Peach MJ. Renin-angiotensin system: biochemistry and mechanisms of action. Physiol Rev. 1977;57:313-70. https://doi.org/10.1152/physrev.1977.57.2.313
  12. Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003;12:70-88. https://doi.org/10.1080/08037050310001057
  13. Crandall DL, Herzlinger HE, Saunders BD, Armellino DC, Kral JG. Distribution of angiotensin II receptors in rat and human adipocytes. J Lipid Res. 1994;35:1378-85. https://doi.org/10.1016/S0022-2275(20)40079-3
  14. Jones BH, Standridge MK, Taylor JW, Moustaid N. Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control. Am J Physiol. 1997;273:R236-42.
  15. Jonsson JR, Game PA, Head RJ, Frewin DB. The expression and localisation of the angiotensin-converting enzyme mRNA in human adipose tissue. Blood Press. 1994;3:72-5. https://doi.org/10.3109/08037059409101524
  16. Danser AH, Schalekamp MA, Bax WA, van den Brink AM, Saxena PR, Riegger GA, Schunkert H. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation. 1995;92:1387-8. https://doi.org/10.1161/01.CIR.92.6.1387
  17. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990;86:1343-6. https://doi.org/10.1172/JCI114844
  18. Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992;359:641-4. https://doi.org/10.1038/359641a0
  19. Hadjadj S, Belloum R, Bouhanick B, Gallois Y, Guilloteau G, Chatellier G, Alhenc-Gelas F, Marre M. Prognostic value of angiotensin-I converting enzyme I/D polymorphism for nephropathy in type 1 diabetes mellitus: a prospective study. J Am Soc Nephrol. 2001;12:541-9. https://doi.org/10.1681/ASN.V123541
  20. Di Pasquale P, Cannizzaro S, Scalzo S, Maringhini G, Pipitone F, Fasullo S, Giubilato A, Ganci F, Vitale G, Sarullo FM, Paterna S. Cardiovascular effects of I/D angiotensin-converting enzyme gene polymorphism in healthy subjects. Findings after follow-up of six years. Acta Cardiol. 2005;60:427-35. https://doi.org/10.2143/AC.60.4.2004993
  21. Sun C, Ponsonby AL, Carlin JB, Bui M, Magnussen CG, Burns TL, Lehtimaki T, Wardrop NH, Juonala M, Viikari JSA, Venn AJ, Raitakari OT, Dwyer T. Childhood adiposity, adult adiposity, and the ACE gene insertion/deletion polymorphism: evidence of gene-environment interaction effects on adult blood pressure and hypertension status in adulthood. J Hypertens. 2018;36:2168-76. https://doi.org/10.1097/HJH.0000000000001816
  22. Um JY, Mun KS, An NH, Kim PG, Kim SD, Song YS, Lee KN, Lee KM, Wi DH, You YO, Kim HM. Polymorphism of angiotensin-converting enzyme gene and BMI in obese Korean women. Clin Chim Acta. 2003;328:173-8. https://doi.org/10.1016/S0009-8981(02)00428-X
  23. Kim K. Association of angiotensin-converting enzyme insertion/deletion polymorphism with obesity, cardiovascular risk factors and exercise-mediated changes in Korean women. Eur J Appl Physiol. 2009;105:879-87. https://doi.org/10.1007/s00421-008-0973-6
  24. Yang SJ, Kim S, Park H, Kim SM, Choi KM, Lim Y, Lee M. Sex-dependent association between angiotensin-converting enzyme insertion/deletion polymorphism and obesity in relation to sodium intake in children. Nutrition. 2013;29:525-30. https://doi.org/10.1016/j.nut.2012.09.001
  25. Thomas GN, Critchley JA, Tomlinson B, Lee ZS, Young RP, Cockran CS, Chan JC. Albuminuria and the renin-angiotensin system gene polymorphisms in type-2-diabetic and in normoglycemic hypertensive Chinese. Clin Nephrol. 2001;55:7-15.
  26. Shan J, Shi Y, Fu G. [The relationship between angiotensin converting enzyme gene polymorphism and risk factors for coronary heart disease]. Zhonghua Liu Xing Bing Xue Za Zhi. 2000;21:208-11.
  27. Uemura K, Nakura J, Kohara K, Miki T. Association of ACE I/D polymorphism with cardiovascular risk factors. Hum Genet. 2000;107:239-42. https://doi.org/10.1007/s004390000358
  28. Lemes VA, Neves AL, Guazzelli IC, Frazzatto E, Nicolau C, Correa-Giannella ML, Velho G, Villares SM. Angiotensin converting enzyme insertion/deletion polymorphism is associated with increased adiposity and blood pressure in obese children and adolescents. Gene. 2013;532:197-202. https://doi.org/10.1016/j.gene.2013.09.065
  29. Strazzullo P, Iacone R, Iacoviello L, Russo O, Barba G, Russo P, D'Orazio A, Barbato A, Cappuccio FP, Farinaro E, Siani A; Olivetti Prospective Heart Study. Genetic variation in the renin-angiotensin system and abdominal adiposity in men: the Olivetti Prospective Heart Study. Ann Intern Med. 2003;138:17-23. https://doi.org/10.7326/0003-4819-138-1-200301070-00007
  30. Kramer H, Wu X, Kan D, Luke A, Zhu X, Adeyemo A, McKenzie C, Cooper R. Angiotensin-converting enzyme gene polymorphisms and obesity: an examination of three black populations. Obes Res. 2005;13:823-8. https://doi.org/10.1038/oby.2005.94
  31. Seo MH, Lee WY, Kim SS, Kang JH, Kang JH, Kim KK, Kim BY, Kim YH, Kim WJ, Kim EM, Kim HS, Shin YA, Shin HJ, Lee KR, Lee KY, Lee SY, Lee SK, Lee JH, Lee CB, Chung S, Cho YH, Choi KM, Han JS, Yoo SJ; Committee of Clinical Practice Guidelines, Korean Society for the Study of Obesity (KSSO). 2018 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea. J Obes Metab Syndr. 2019;28:40-5. https://doi.org/10.7570/jomes.2019.28.1.40
  32. Koch W, Latz W, Eichinger M, Ganser C, Schomig A, Kastrati A. Genotyping of the angiotensin I-converting enzyme gene insertion/deletion polymorphism by the TaqMan method. Clin Chem. 2005;51:1547-9. https://doi.org/10.1373/clinchem.2005.051656
  33. Jones BH, Standridge MK, Moustaid N. Angiotensin II increases lipogenesis in 3T3-L1 and human adipose cells. Endocrinology. 1997;138:1512-9. https://doi.org/10.1210/en.138.4.1512
  34. Pan YH, Wang M, Huang YM, Wang YH, Chen YL, Geng LJ, Zhang XX, Zhao HL. ACE Gene I/D Polymorphism and Obesity in 1,574 Patients with Type 2 Diabetes Mellitus. Dis Markers. 2016;2016:7420540. https://doi.org/10.1155/2016/7420540
  35. Xi B, Ruiter R, Chen J, Pan H, Wang Y, Mi J. The ACE insertion/deletion polymorphism and its association with metabolic syndrome. Metabolism. 2012;61:891-7. https://doi.org/10.1016/j.metabol.2011.10.022
  36. Kim K, Ahn N, Park J, Koh J, Jung S, Kim S, Moon S. Association of angiotensin-converting enzyme I/D and alpha-actinin-3 R577X genotypes with metabolic syndrome risk factors in Korean children. Obes Res Clin Pract. 2016;10 Suppl 1:S125-32. https://doi.org/10.1016/j.orcp.2015.09.008
  37. Thomas GN, Tomlinson B, Chan JC, Sanderson JE, Cockram CS, Critchley JA. Renin-angiotensin system gene polymorphisms, blood pressure, dyslipidemia, and diabetes in Hong Kong Chinese: a significant association of tne ACE insertion/deletion polymorphism with type 2 diabetes. Diabetes Care. 2001;24:356-61. https://doi.org/10.2337/diacare.24.2.356
  38. Singh RK, Kumar P, Mahalingam K. Molecular genetics of human obesity: A comprehensive review. C R Biol. 2017;340:87-108. https://doi.org/10.1016/j.crvi.2016.11.007