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Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis

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Abstract

SLE is a systemic autoimmune disease with high prevalence of hypertension. Around 40–75 % of SLE patients develop nephritis, a major cause of hypertension and mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16 of ACE gene was reported to influence the development of hypertension, nephritis, and cardiovascular diseases in different ethnic populations. Despite compelling evidence for the high prevalence of hypertension in individuals with SLE, underlying factors for its development are not well studied. With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients. Three hundred patients with SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls, respectively. The ACE gene insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion (D) alleles were observed to be equally distributed among patients (57 and 43 %) and controls (59 and 41 %), respectively. The mutant (D) allele did not confer significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8–1.6; II vs. DD: p = 0.34, OR 1.22, 95 % CI 0.8–1.85). There was no association of the ACE genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19, OR 1.41, 95 % CI 0.84–2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38–1.41) or hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43–1.8; II vs. DD: p = 0.66, OR 1.217, 95 % CI 0.5–2.8). The presence of mutant allele (D) was not found to influence any clinical features or autoantibody phenotype. The insertion/deletion polymorphism of the ACE gene is not a genetic risk factor for SLE and does not influence development of hypertension or lupus nephritis in South Indian Tamils.

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Abbreviations

ACE:

Angiotensin-converting enzyme

SLE:

Systemic lupus erythematosus

ACR:

American College of Rheumatology

LN:

Lupus nephritis

SEM:

Standard error of mean

SD:

Standard deviation

References

  1. Wakeland EK, Liu K, Graham RR, Behrens TW (2001) Delineating the genetic basis of SLE. Immunity 15:397–408

    Article  CAS  PubMed  Google Scholar 

  2. Canetta PA, Bomback AS, Radhakrishnan J (2011) Treating lupus in the kidney: where are we now, and where are we going? Discov Med 12:341–349

    PubMed  Google Scholar 

  3. Ramu P, Umamaheswaran G, Shewade DG, Swaminathan RP, Dutta TK, Balachander J, Adithan C (2011) Candidate gene polymorphisms of renin angiotensin system and essential hypertension in south Indian Tamilian population. Int J Hum Genet 11:31–40

    CAS  Google Scholar 

  4. Cambien F, Alhenc-Gelas F, Herbeth B, Andre JL, Rakotovao R, Gonzales MF, Allegrini J, Bloch C (1988) Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study. Am J Hum Genet 43:774–780

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F (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 

  6. Tabatabaei FAS, Oostra BA, Isaacs AM, Van Duijn CM, Witteman JCM (2006) ACE polymorphisms. Circ Res 98:1123–1133

    Article  Google Scholar 

  7. Ryan MJ (2009) The pathophysiology of hypertension in systemic lupus erythematosus. Am J Physiol Regul Integr Comp Physiol 296:R1258–R1267

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  CAS  PubMed  Google Scholar 

  9. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640

    Article  CAS  PubMed  Google Scholar 

  10. Markowitz GS, D’Agati VD (2007) The ISN/RPS 2003 classification of lupus nephritis: an assessment at 3 years. Kidney Int 71:491–495

    Article  CAS  PubMed  Google Scholar 

  11. Chobanian AV, George LB, Henry RB et al (2003) The Seventh Report of the Joint National Committee on report prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 289:2560–2571

    Article  CAS  PubMed  Google Scholar 

  12. Miller SA, Dykes DD, Polesky HF (1988) Simple salting out procedure for extracting DNA from human nucleated cells. Nuc Acids Res 16:1215

    Article  CAS  Google Scholar 

  13. Patel M, Clarke AM, Bruce IN, Symmons DP (2006) The prevalence and incidence of biopsy-proven lupus nephritis in the UK: evidence of an ethnic gradient. Arthritis Rheum 54:2963–2969

    Article  PubMed  Google Scholar 

  14. Tassiulas IO, Aksentijevich I, Salmon JE, Kim Y, Yarboro CH, Vaughan EM et al (1998) Angiotensin I converting enzyme gene polymorphisms in systemic lupus erythematosus: decreased prevalence of DD genotype in African American patients. Clin Nephrol 50:8–13

    CAS  PubMed  Google Scholar 

  15. Malaviya AN, Chandrasekaran AN, Kumar A, Shamar PN (1997) Systemic lupus erythematosus in India. Lupus 6:690–700

    Article  CAS  PubMed  Google Scholar 

  16. Remuzzi G, Perico N, Macia M, And Ruggenenti P. The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int 2005;68 9 (Suppl 99): pp. S57–S6

  17. Sprovieri SR, Sens YA (2005) Polymorphisms of the renin-angiotensin system genes in Brazilian patients with lupus nephropathy. Lupus 14:356–362

    Article  CAS  PubMed  Google Scholar 

  18. Molad Y, Gal E, Magal N, Sulkes J 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 30:132–137

    Article  CAS  PubMed  Google Scholar 

  19. Prkacin I, Novak B, Sertić J, Mrzljak A (2001) Angiotensin-converting enzyme gene polymorphism in patients with systemic lupus. Acta Med Croatica 55:73–76

    CAS  PubMed  Google Scholar 

  20. Akai Y, Sato H, Iwano M, Kurumatani N, Kurioka H, Kubo A et al (1999) Association of an insertion polymorphism of angiotensin-converting enzyme gene with the activity of lupus nephritis. Clin Nephrol 51:141–146

    CAS  PubMed  Google Scholar 

  21. Zhou TB, Liu YG, Lin N, Qin YH, Huang K, Shao MB, Peng DD (2012) Relationship between angiotensin-converting enzyme insertion/deletion gene polymorphism and systemic lupus erythematosus/lupus nephritis: a systematic review and metaanalysis. J Rheumatol 39:686–693

    Article  CAS  PubMed  Google Scholar 

  22. Topete-Reyes JF, SotoVargas J, Morán Moguel MC, Dávalos-Rodríguez (2013) Insertion/deletion polymorphism of the angiotensin-converting enzyme gene in lupus nephritis among Mexicans. Immunopharmacol Immunotoxicol 35:174–180

    Article  CAS  PubMed  Google Scholar 

  23. Pullmann RJ, Lukac J, Skerenova M, Rovensky J, Hybenova J, Melus V et al (1999) Association between systemic lupus erythematosus and insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene. Clin Exp Rheumatol 17:593–596

    PubMed  Google Scholar 

  24. Uhm WS, Lee HS, Chung YH, Kim TH et al (2002) Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE. Lupus 11:227–233

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was funded by the Department of Science and Technology, Govt. of India, New Delhi (Grant No. SR/SO/HS-67/2004 dated 03.08.2007).

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Authors and Affiliations

  1. Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India

    Vir S. Negi & Panneer Devaraju

  2. Genetic services Unit, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India

    Reena Gulati

Authors
  1. Vir S. Negi
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  2. Panneer Devaraju
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  3. Reena Gulati
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Correspondence to Vir S. Negi.

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Negi, V.S., Devaraju, P. & Gulati, R. Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis. Clin Rheumatol 34, 1545–1549 (2015). https://doi.org/10.1007/s10067-015-2954-6

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  • DOI: https://doi.org/10.1007/s10067-015-2954-6

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