Molecular Biology Reports

, Volume 39, Issue 10, pp 9485–9491 | Cite as

Association study of ACE polymorphisms and systemic lupus erythematosus in Northern Chinese Han population

  • Ai-min Gong
  • Xin-yuan Li
  • Yi-qin Wang
  • Hai-xia Yan
  • Zhao-xia Xu
  • Zhao Feng
  • Yi-qiang Xie
  • De-hui Yin
  • Shi-zhong Yang


Systemic lupus erythematosus (SLE) is an autoimmune disease, with multiple genetic and environmental factors involving in its etiology. Angiotensin converting enzyme (ACE) gene was reported to have important roles in the development and progression of SLE. In this study, a case–control study was carried out to investigate the effects of seven SNPs and I/D in ACE gene in the development of SLE in Northern China. Seven SNPs including A5466C, T3892C, A240T, C1237T, G2215A, A2350G and C3409T were genotyped by PCR-RFLP method, and I/D was examined by agarose gel electrophoresis followed PCR directly. 314 SLE patients were compared to 320 normal controls in the study. Data were analyzed by SPSS 13.0 and HaploView software. The frequency distribution of SNP A2350G and Alu I/D and five haplotypes (AAAACCCI, AGAACCTD, AAAATCTI, TAAATTTI and TAAATCTI) were demonstrated to be different between case and control groups significantly. Whereas other SNPs and haplotypes had no differences in two cohorts. The results revealed that variations of ACE gene had association with SLE, which indicated ACE gene may play an important role in pathogenesis of SLE in Northern Chinese Han population.


ACE SLE Polymorphism Association 



We greatly acknowledge the numerous donors for making this work possible. We thank the corresponding people of Harbin Medical University, Hainan Medical University and Shanghai University of Traditional Chinese.

Conflict of interest



  1. 1.
    Tan FK, Arnett FC (1998) The genetics of lupus. Curr Opin Rheumatol 10(5):399–408PubMedCrossRefGoogle Scholar
  2. 2.
    Guerra SG et al (2011) Dense mapping of IL18 shows no association in SLE. Hum Mol Genet 20(5):1026–1033PubMedCrossRefGoogle Scholar
  3. 3.
    Kyogoku C et al (2004) Genetic association of the R620 W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 75(3):504–507PubMedCrossRefGoogle Scholar
  4. 4.
    Lee HS et al (2007) Association of STAT4 with rheumatoid arthritis in the Korean population. Mol Med 13(9–10):455–460PubMedGoogle Scholar
  5. 5.
    Remmers EF et al (2007) STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 357(10):977–986PubMedCrossRefGoogle Scholar
  6. 6.
    Xu J et al (2007) Association of ACE gene polymorphism with genetic susceptibility to systemic lupus erythematosus in a Chinese population: a family-based association study. J Rheumatol 34(12):2408–2411PubMedGoogle Scholar
  7. 7.
    Parsa A et al (2002) Association of angiotensin-converting enzyme polymorphisms with systemic lupus erythematosus and nephritis: analysis of 644 SLE families. Genes Immun 3(Suppl 1):S42–S46PubMedCrossRefGoogle Scholar
  8. 8.
    Uhm WS et al (2002) Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE. Lupus 11(4):227–233PubMedCrossRefGoogle Scholar
  9. 9.
    Kaufman KM et al (2001) Linkage analysis of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and systemic lupus erythematosus. Mol Cell Endocrinol 177(1–2):81–85PubMedCrossRefGoogle Scholar
  10. 10.
    Nataraj C et al (1999) Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. J Clin Invest 104(12):1693–1701PubMedCrossRefGoogle Scholar
  11. 11.
    Suzuki Y, Ruiz-Ortega M, Egido J (2000) Angiotensin II: a double-edged sword in inflammation. J Nephrol 13(Suppl 3):S101–S110PubMedGoogle Scholar
  12. 12.
    Taal MW et al (2000) Cellular and molecular mediators in common pathway mechanisms of chronic renal disease progression. Curr Opin Nephrol Hypertens 9(4):323–331PubMedCrossRefGoogle Scholar
  13. 13.
    Molad Y et al (2000) Renal outcome and vascular morbidity in systemic lupus erythematosus (SLE): lack of association with the angiotensin-converting enzyme gene polymorphism. Semin Arthritis Rheum 30(2):132–137PubMedCrossRefGoogle Scholar
  14. 14.
    Egido J (1996) Vasoactive hormones and renal sclerosis. Kidney Int 49(2):578–597PubMedCrossRefGoogle Scholar
  15. 15.
    Sprovieri SR, Sens YA (2005) Polymorphisms of the renin-angiotensin system genes in Brazilian patients with lupus nephropathy. Lupus 14(5):356–362PubMedCrossRefGoogle Scholar
  16. 16.
    Lee YH et al (2006) Angiotensin-converting enzyme insertion/deletion polymorphism and systemic lupus erythematosus: a metaanalysis. J Rheumatol 33(4):698–702PubMedGoogle Scholar
  17. 17.
    Schena FP et al (2001) ACE gene polymorphism and IgA nephropathy: an ethnically homogeneous study and a meta-analysis. Kidney Int 60(2):732–740PubMedCrossRefGoogle Scholar
  18. 18.
    Chuang LM et al (1997) Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with hypertension, non-insulin-dependent diabetes mellitus, and coronary heart disease in Taiwan. Metabolism 46(10):1211–1214PubMedCrossRefGoogle Scholar
  19. 19.
    Gutierrez C et al (1997) Angiotensin I-converting enzyme and angiotensinogen gene polymorphisms in non-insulin-dependent diabetes mellitus. Lack of relationship with diabetic nephropathy and retinopathy in a Caucasian Mediterranean population. Metabolism 46(8):976–980PubMedCrossRefGoogle Scholar
  20. 20.
    Li X et al (2010) Association of the genetic polymorphisms of the ACE gene and the eNOS gene with lupus nephropathy in Northern Chinese population. BMC Med Genet 11:94PubMedCrossRefGoogle Scholar
  21. 21.
    Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725PubMedCrossRefGoogle Scholar
  22. 22.
    Rupert JL et al (2003) Genetic polymorphisms in the renin–angiotensin system in high-altitude and low-altitude Native American populations. Ann Hum Genet 67(Pt 1):17–25PubMedCrossRefGoogle Scholar
  23. 23.
    Koehle MS et al (2006) No association between variants in the ACE and angiotensin II receptor 1 genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima festival at 4,380 m. High Alt Med Biol 7(4):281–289PubMedCrossRefGoogle Scholar
  24. 24.
    Zhu X et al (2001) Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure. Am J Hum Genet 68(5):1139–1148PubMedCrossRefGoogle Scholar
  25. 25.
    Qi Y et al (2008) Synergistic effect of the genetic polymorphisms of the renin–angiotensin–aldosterone system on high-altitude pulmonary edema: a study from Qinghai-Tibet altitude. Eur J Epidemiol 23(2):143–152PubMedCrossRefGoogle Scholar
  26. 26.
    Gaffney PM et al (2000) Genome screening in human systemic lupus erythematosus: results from a second Minnesota cohort and combined analyses of 187 sib-pair families. Am J Hum Genet 66(2):547–556PubMedCrossRefGoogle Scholar
  27. 27.
    Erdos EG (1976) Conversion of angiotensin I to angiotensin II. Am J Med 60(6):749–759PubMedCrossRefGoogle Scholar
  28. 28.
    Nawaz SK, Hasnain S (2011) Effect of ACE polymorphisms on the association between noise and hypertension in a Pakistani population. J Renin Angiotensin Aldosterone SystGoogle Scholar
  29. 29.
    Rigat B 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(4):1343–1346PubMedCrossRefGoogle Scholar
  30. 30.
    Pullmann R Jr et al (1999) Association between systemic lupus erythematosus and insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene. Clin Exp Rheumatol 17(5):593–596PubMedGoogle Scholar
  31. 31.
    Douglas G et al (2004) Angiotensin-converting enzyme (insertion/deletion) and endothelial nitric oxide synthase polymorphisms in patients with systemic lupus erythematosus. J Rheumatol 31(9):1756–1762PubMedGoogle Scholar
  32. 32.
    Kennon B et al (1999) Angiotensin-converting enzyme gene and diabetes mellitus. Diabet Med 16(6):448–458PubMedCrossRefGoogle Scholar
  33. 33.
    Tassiulas IO et al (1998) Angiotensin I converting enzyme gene polymorphisms in systemic lupus erythematosus: decreased prevalence of DD genotype in African-American patients. Clin Nephrol 50(1):8–13PubMedGoogle Scholar
  34. 34.
    Wipff J et al (2009) Angiotensin-converting enzyme gene does not contribute to genetic susceptibility to systemic sclerosis in European Caucasians. J Rheumatol 36(2):337–340PubMedCrossRefGoogle Scholar
  35. 35.
    Chan IH et al (2006) Gene–gene interactions for asthma and plasma total IgE concentration in Chinese children. J Allergy Clin Immunol 117(1):127–133PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Ai-min Gong
    • 1
  • Xin-yuan Li
    • 2
  • Yi-qin Wang
    • 3
  • Hai-xia Yan
    • 3
  • Zhao-xia Xu
    • 3
  • Zhao Feng
    • 1
  • Yi-qiang Xie
    • 1
  • De-hui Yin
    • 4
  • Shi-zhong Yang
    • 4
  1. 1.Department of Internal Medicine of Traditional Chinese MedicineHainan Medical UniversityHaikouPeople’s Republic of China
  2. 2.Department of RheumatologyThe Second Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  3. 3.School of Basic MedicineShanghai University of Traditional ChineseShanghaiPeople’s Republic of China
  4. 4.Department of Health Preservation and RehabilitationHainan Medical UniversityHaikouPeople’s Republic of China

Personalised recommendations