Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1996 Aug;51(8):777–780. doi: 10.1136/thx.51.8.777

Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis.

K Furuya 1, E Yamaguchi 1, A Itoh 1, N Hizawa 1, N Ohnuma 1, J Kojima 1, N Kodama 1, Y Kawakami 1
PMCID: PMC472533  PMID: 8795663

Abstract

BACKGROUND: Genetic control of serum angiotensin I converting enzyme (SACE) levels has been suggested. A study was undertaken to elucidate the role of this polymorphism in sarcoidosis. METHODS: Three hundred and forty one unrelated healthy controls and 103 consecutive patients with sarcoidosis participated in the study. SACE levels and an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene were studied in each subject and new reference intervals for SACE activity for each genotype were determined. The difference in genotype and allele frequencies between controls and patients was analysed and odds ratios were calculated to estimate the relative risk. RESULTS: A significant association was seen between ACE gene polymorphism and SACE levels in both patients and controls. The new reference intervals for each genotype discriminated abnormal SACE levels in patients more accurately, especially those with genotype II. In women the frequencies of allele I were 0.68 (allele D 0.32) in controls and 0.58 (allele D 0.42) in patients, and the difference between the two female groups was significant (p < 0.05). Thus, an excess of genotype ID or DD was observed in female patients (odds ratio 2.18; 95% confidence interval 1.18 to 4.01; p = 0.01). CONCLUSIONS: These findings suggest that ACE gene polymorphism is associated with SACE levels in both patients with sarcoidosis and controls. ACE gene polymorphism should be further evaluated as a candidate marker for an increased risk of sarcoidosis.

Full text

PDF
777

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cambien F., Alhenc-Gelas F., Herbeth B., Andre J. L., Rakotovao R., Gonzales M. F., Allegrini J., Bloch C. Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study. Am J Hum Genet. 1988 Nov;43(5):774–780. [PMC free article] [PubMed] [Google Scholar]
  2. Cambien F., Poirier O., Lecerf L., Evans A., Cambou J. P., Arveiler D., Luc G., Bard J. M., Bara L., Ricard S. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992 Oct 15;359(6396):641–644. doi: 10.1038/359641a0. [DOI] [PubMed] [Google Scholar]
  3. Costerousse O., Allegrini J., Lopez M., Alhenc-Gelas F. Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J. 1993 Feb 15;290(Pt 1):33–40. doi: 10.1042/bj2900033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Da Costa J. L. Geographic epidemiology of sarcoidosis in southeast Asia. Am Rev Respir Dis. 1973 Nov;108(5):1269–1272. doi: 10.1164/arrd.1973.108.5.1269. [DOI] [PubMed] [Google Scholar]
  5. Fogarty Y., Fraser C. G., Browning M. C. Intra- and inter-individual variation of serum angiotensin converting enzyme: clinical implications. Ann Clin Biochem. 1989 Mar;26(Pt 2):201–202. doi: 10.1177/000456328902600224. [DOI] [PubMed] [Google Scholar]
  6. Furuya K., Yamaguchi E., Hirabayashi T., Itoh A., Hizawa N., Ohnuma N., Kawakami Y. Angiotensin-I-converting enzyme gene polymorphism and susceptibility to cough. Lancet. 1994 Feb 5;343(8893):354–354. doi: 10.1016/s0140-6736(94)91190-8. [DOI] [PubMed] [Google Scholar]
  7. Kasahara Y., Ashihara Y. Colorimetry of angiotensin-I converting enzyme activity in serum. Clin Chem. 1981 Nov;27(11):1922–1925. [PubMed] [Google Scholar]
  8. Kozlowski S., Corr M., Shirai M., Boyd L. F., Pendleton C. D., Berzofsky J. A., Margulies D. H. Multiple pathways are involved in the extracellular processing of MHC class I-restricted peptides. J Immunol. 1993 Oct 15;151(8):4033–4044. [PubMed] [Google Scholar]
  9. Kozlowski S., Corr M., Takeshita T., Boyd L. F., Pendleton C. D., Germain R. N., Berzofsky J. A., Margulies D. H. Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules. J Exp Med. 1992 Jun 1;175(6):1417–1422. doi: 10.1084/jem.175.6.1417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lee E. J. Population genetics of the angiotensin-converting enzyme in Chinese. Br J Clin Pharmacol. 1994 Feb;37(2):212–214. doi: 10.1111/j.1365-2125.1994.tb04264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lieberman J. Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med. 1975 Sep;59(3):365–372. doi: 10.1016/0002-9343(75)90395-2. [DOI] [PubMed] [Google Scholar]
  12. Lieberman J., Nosal A., Schlessner A., Sastre-Foken A. Serum angiotensin-converting enzyme for diagnosis and therapeutic evaluation of sarcoidosis. Am Rev Respir Dis. 1979 Aug;120(2):329–335. doi: 10.1164/arrd.1979.120.2.329. [DOI] [PubMed] [Google Scholar]
  13. MAYOCK R. L., BERTRAND P., MORRISON C. E., SCOTT J. H. MANIFESTATIONS OF SARCOIDOSIS. ANALYSIS OF 145 PATIENTS, WITH A REVIEW OF NINE SERIES SELECTED FROM THE LITERATURE. Am J Med. 1963 Jul;35:67–89. doi: 10.1016/0002-9343(63)90165-7. [DOI] [PubMed] [Google Scholar]
  14. Neels H. M., Scharpé S. L., van Sande M. E., Verkerk R. M., Van Acker K. J. Improved micromethod for assay of serum angiotensin converting enzyme. Clin Chem. 1982 Jun;28(6):1352–1355. [PubMed] [Google Scholar]
  15. Okabe T., Yamagata K., Fujisawa M., Watanabe J., Takaku F., Lanzillo J. J., Fanburg B. L. Increased angiotensin-converting enzyme in peripheral blood monocytes from patients with sarcoidosis. J Clin Invest. 1985 Mar;75(3):911–914. doi: 10.1172/JCI111791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pertschuk L. P., Silverstein E., Friedland J. Immunohistologic diagnosis of sarcoidosis. Detection of angiotensin-converting enzyme in sarcoid granulomas. Am J Clin Pathol. 1981 Mar;75(3):350–354. doi: 10.1093/ajcp/75.3.350. [DOI] [PubMed] [Google Scholar]
  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 Oct;86(4):1343–1346. doi: 10.1172/JCI114844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rigat B., Hubert C., Corvol P., Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res. 1992 Mar 25;20(6):1433–1433. doi: 10.1093/nar/20.6.1433-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sherman L. A., Burke T. A., Biggs J. A. Extracellular processing of peptide antigens that bind class I major histocompatibility molecules. J Exp Med. 1992 May 1;175(5):1221–1226. doi: 10.1084/jem.175.5.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Silberstein L. E., Berkman E. M., Fanburg B. L. Angiotensin-1-converting enzyme (ACE) activity in human serum following plasma exchange. Proc Soc Exp Biol Med. 1983 Jun;173(2):222–226. doi: 10.3181/00379727-173-41635. [DOI] [PubMed] [Google Scholar]
  21. Soubrier F., Alhenc-Gelas F., Hubert C., Allegrini J., John M., Tregear G., Corvol P. Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9386–9390. doi: 10.1073/pnas.85.24.9386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weinstock J. V., Blum A. M., Kassab J. T. Angiotensin II is chemotactic for a T-cell subset which can express migration inhibition factor activity in murine schistosomiasis mansoni. Cell Immunol. 1987 Jun;107(1):180–187. doi: 10.1016/0008-8749(87)90278-4. [DOI] [PubMed] [Google Scholar]
  23. Weinstock J. V., Kassab J. Chemotactic response of splenic mononuclear cells to angiotensin II in murine schistosomiasis. J Immunol. 1986 Sep 15;137(6):2020–2024. [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES