Skip to main content
Log in

Association between the ACE gene I/D polymorphism and osteoporosis in a Turkish population

Verbindung zwischen dem I/D-Polymorphismus des ACE-Gens und Osteoporose in einer türkischen Population

  • Originalien
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to assess the relationship between osteoporosis and the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in a Turkish population.

Methods

The study group consisted of 238 unrelated women with osteoporosis and 124 unrelated healthy female controls. All participants, patients and healthy controls, were of Turkish origin from the central region of Turkey. Genomic DNA was isolated from whole venous blood samples using a commercial DNA isolation kit. The ACE gene I/D polymorphism was analysed by polymerase chain reaction and gel electrophoresis.

Results

Frequencies of the DD, ID and II genotypes in the patients were 44.5, 41.2 and 14.3 %, and in the controls they were 25.0, 51.6 and 23.4 %, respectively. A significant difference was observed between patients and controls according to genotype frequency (p = 0.001). D and I allele frequencies of the I/D polymorphism were 65.1 and 34.9 % in the patient group and 50.8 and 49.2 % in the control group, respectively (p < 0.001).

Conclusion

The ACE gene I/D polymorphism could be a genetic factor associated with osteoporosis.

Zusammenfassung

Ziel

Ziel dieser Studie war es, die Verbindung zwischen Osteoporose und dem Insertion/Deletion(I/D)-Polymorphismus des Angiotensin-konvertierenden-Enzym(ACE)-Gens in einer türkischen Population zu untersuchen.

Methoden

Die Studiengruppe bestand aus 238 nichtverwandten Frauen mit Osteoporose und einer Kontrollgruppe mit 124 nichtverwandten gesunden Frauen. Alle Teilnehmenden, die Patienten und die gesunde Kontrollgruppe, stammten aus der Zentraltürkei. Mittels eines handelsüblichen DNA-Isolationskits wurde aus venösen Blutproben genomische DNA entnommen. Der ACE-I/D-Polymorphismus wurde mittels Polymerase-Kettenreaktion und Gelelektrophorese analysiert.

Ergebnisse

Die Häufigkeiten der Genotypen DD, ID und II in den Patienten waren 44,5, 41,2 und 14,3 %, in der Kontrollgruppe betrugen sie 25,0, 51,6 und 23,4 %. Es wurde ein signifikanter Unterschied zwischen den Patienten und der Kontrollgruppe bezüglich der Genotyp-Häufigkeit (p = 0,001) beobachtet. Die Häufigkeiten der Allelen D und I der I/D-Polymorphismen betrugen 65,1 und 34,9 % in der Patientengruppe bzw. 50,8 und 49,2 % in der Kontrollgruppe (p < 0,001).

Conclusion

Beim I/D-Polymorphismus des ACE-Gens könnte es sich um einen genetischen Faktor handeln, der mit Osteoporose assoziiert ist.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Genant HK, Cooper C, Poor G et al (1999) Interim report and recommendations of the World Health Organization task-force for osteoporosis. Osteoporos Int 10:259–264

    Article  CAS  PubMed  Google Scholar 

  2. Cooper C, Melton LJ (1992) Epidemiology of osteoporosis. Trends Endocrinol Metab 3:224–229

    Article  CAS  PubMed  Google Scholar 

  3. Gennari L, Becherini L, Falchetti A et al (2002) Genetics of osteoporosis: role of steroid hormone receptor gene polymorphisms. J Steroid Biochem Mol Biol 81:1–24

    Article  CAS  PubMed  Google Scholar 

  4. Soroko SB, Barrett-Connor E, Edelstein SL, Kritz-Silverstain D (1994) Family history of osteoporosis and bone mineral density at the axial skeleton: the Rancho Bernardo study. J Bone Miner Res 9:761–769

    Article  CAS  PubMed  Google Scholar 

  5. Diaz MN, O’Neill TW, Silman AJ (1997) The influence of family history of hip fracture on the risk of vertebral deformity in men and women: the European Vertebral Osteoporosis study. Bone 20:145–149

    Article  CAS  PubMed  Google Scholar 

  6. Hardy R, Cooper MS (2009) Bone loss in inflammatory disorders. J Endocrinol 201:309–320

    Article  CAS  PubMed  Google Scholar 

  7. Mendoza-Pinto C, Garcia-Carrasco M, Jimenez-Hernandez M et al (2010) Etiopathogenesis of Behcet’s disease. Autoimmun Rev 9:241–245

    Article  CAS  PubMed  Google Scholar 

  8. Ruiz-Ortega M, Lorenzo O, Suzuki Y et al (2001) Proinflammatory actions of angiotensins. Curr Opin Nephrol Hypertens 10:321–329

    Article  CAS  PubMed  Google Scholar 

  9. Hubert C, Houot AM, Corvol P, Soubrier F (1991) Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem 266:15377–15383

    CAS  PubMed  Google Scholar 

  10. Glenn KL, Du ZQ, Eisenmann JC, Rothschild MF (2009) An alternative method for genotyping of the ACE I/D polymorphism. Mol Biol Rep 366:1305–1310

    Article  Google Scholar 

  11. Kritchevsky SB, Nicklas BJ, Visser M et al (2005) Angiotensin-converting enzyme insertion/deletion genotype, exercise and physical decline. JAMA 294:691–698

    Article  CAS  PubMed  Google Scholar 

  12. Tiret L, Rigat B, Visvikis S et al (1992) Evidence from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 51:197–205

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Lehmann DJ, Cortina-Borja M, Warden DR et al (2005) Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am J Epidemiol 162:305–317

    Article  PubMed  Google Scholar 

  14. Yigit S, Tural S, Rustemoglu A et al (2013) DD genotype of ACE gene I/D polymorphism is associated with Behcet disease in a Turkish population. Mol Biol Rep 40:365–368

    Article  CAS  PubMed  Google Scholar 

  15. Nacak M, Erbagci Z, Buyukafsar K et al (2007) Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with allergic contact dermatitis. Basic Clin Pharmacol Toxicol 101:101–103

    Article  CAS  PubMed  Google Scholar 

  16. Shehab DK, Al-Jarallah KF, Alawadhi AM et al (2008) Prevalence of angiotensin-converting enzyme gene insertion–deletion polymorphism in patients with primary knee osteoarthritis. Clin Exp Rheumatol 26:305–310

    CAS  PubMed  Google Scholar 

  17. Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO study group. Osteoporos Int 4:368–381

    Article  CAS  PubMed  Google Scholar 

  18. Swanberg M, McGuigan F, Ivaska KK et al (2010) Polymorphisms in the macrophage migration inhibitory factor gene and bone loss in postmenopausal women. Bone 47:424–429

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Peng YM, Lei SF, Guo Y et al (2008) Sex-specific association of the glucocorticoid receptor gene with extreme BMD. J Bone Miner Res 23:247–252

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Arko B, Prezelj J, Kocijancic A et al (2005) Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal women. Maturitas 51:270–279

    Article  CAS  PubMed  Google Scholar 

  21. Rigat B, Hubert C, Alhenc-Gelas F et al (1990) An insertion/deletion polymorphism in the angiotensin I converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Shimizu H, Nakagami H, Morishita R (2012) Activation of osteoclasts by RAAS and strategy of target therapy on bone metabolic diseases. Nihon Rinsho 70:1524–1529

    PubMed  Google Scholar 

  23. Shimizu H, Nakagami H, Osako MK et al (2008) Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB J 22:2465–2475

    Article  CAS  PubMed  Google Scholar 

  24. Perez-Castrillon JL, Justo I et al (2003) Relationship between bone mineral density and angiotensin converting enzyme polymorphism in hypertensive postmenopausal women. Am J Hypertens 16:233–235

    Article  CAS  PubMed  Google Scholar 

  25. Perez-Castrillon JL, Silvia J, Justo I et al (2003) Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on the bone mass of hypertensive subjects: relationship with angiotensin converting enzyme polymorphisms. Am J Hypertens 16:453–459

    Article  CAS  PubMed  Google Scholar 

  26. Altun B, Kiykim AA, Seyrantepe V et al (2004) Association between activated renin angiotensin system and bone formation in hemodialysis patients: is the bone mass genetically determined by ACE gene polymorphism? Ren Fail 26:425–431

    Article  CAS  PubMed  Google Scholar 

  27. Zhang Y, Qin L, Leung P, Kwok TCY (2012) The effect of angiotensin-converting enzyme inhibitor use on bone loss in elderly Chinese. J Bone Miner Metab 30:666–673

    Article  CAS  PubMed  Google Scholar 

  28. Bayram B, Sayın E, Gunes HV et al (2011) DD genotype of ace gene I/D polymorphism is associated in a Turkish study population with osteoarthritis. Mol Biol Rep 38:1713–1716

    Article  CAS  PubMed  Google Scholar 

  29. Inanir A, Yigit S, Tural S et al (2013) MTHFR gene C677T mutation and ACE gene I/D polymorphism in Turkish patients with osteoarthritis. Dis Markers 34:17–22

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Yigit S, Inanir A, Tural S, Ates O (2012) Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and rheumatoid arthritis. Gene 511:106–108

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with ethical guidelines

Conflict of interest. B. Cakmak, A. Inanir, N. Karakus, O. Ates and S. Yigit state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to B. Cakmak MD..

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cakmak, B., Inanir, A., Karakus, N. et al. Association between the ACE gene I/D polymorphism and osteoporosis in a Turkish population. Z Rheumatol 74, 346–350 (2015). https://doi.org/10.1007/s00393-015-1582-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-015-1582-5

Keywords

Schlüsselwörter

Navigation