Skip to main content

Advertisement

SpringerLink
Log in

Gene polymorphisms contributing to hypertension in immunoglobulin A nephropathy

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Background

Hypertension, which is affected by genetic and environmental factors, is one of the major risk factors for chronic kidney disease. Identification of the genetic factor contributing to hypertension in patients with chronic kidney disease may potentially refine a therapeutic strategy.

Methods

In the present multicenter cross-sectional study, 240 patients were eligible (aged 15–50 years with urinary protein ≥0.25 g/day) out of 429 patients who were diagnosed as having immunoglobulin (Ig) A nephropathy (IgAN) by renal biopsy between 1990 and 2005 and enrolled in our previous study, PREDICT-IgAN. The outcome was hypertension defined as ≥140 and/or ≥90 mmHg of systolic and diastolic blood pressure and/or use of antihypertensives at renal biopsy. We assessed associations between hypertension and 28 polymorphisms with the frequency of minor genotype ≥10% among 100 atherosclerosis-related polymorphisms using the Chi-squared test in dominant and recessive models. We identified polymorphisms associated with hypertension in multivariate logistic regression models.

Results

Baseline characteristics: hypertension 36.3%. Among 28 polymorphisms, the Chi-squared test revealed that CD14 (-159CC vs CT/TT, P = 0.03) and ACE (DD vs DI/II, P = 0.03) were significantly associated with hypertension after Bonferroni correction. Multivariate logistic regression models revealed that CD14 -159CC [vs CT/TT, odds ratio (OR) 3.58 (95% confidence interval (CI) 1.66–7.63)] and ACE DD [vs DI/II, OR 4.41 (95% CI 1.80–10.8), P = 0.001] were independently associated with hypertension.

Conclusions

CD14 C-159T and ACE I/D contributed to hypertension in patients with IgAN.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barsoum R. Chronic kidney disease in the developing world. N Engl J Med. 2006;354(10):997–9.

    Article  PubMed  CAS  Google Scholar 

  2. System. USRD. USRDS 2008 annual data report: atlas of end-stage renal disease in the United States. National Institute of Diabetes and Digestive and Kidney Diseases, 2008; 2009.

  3. Wiwanitkit V. Angiotensin-converting enzyme gene polymorphism is correlated to the progression of disease in patients with IgA nephropathy: a meta-analysis. Ren Fail. 2006;28(8):697–9.

    Article  PubMed  Google Scholar 

  4. Koomans H, Roos J, Boer P, Geyskes G, Mees E. Salt sensitivity of blood pressure in chronic renal failure. Evidence for renal control of body fluid distribution in man. Hypertension. 1982;4(2):190–7.

    PubMed  CAS  Google Scholar 

  5. Farmer C, Goldsmith D, Cox J, Dallyn P, Kingswood J, Sharpstone P. An investigation of the effect of advancing uraemia, renal replacement therapy and renal transplantation on blood pressure diurnal variability. Nephrol Dial Transplant. 1997;12(11):2301–7.

    Article  PubMed  CAS  Google Scholar 

  6. Hering D, Zdrojewski Z, Król E, Kara T, Kucharska W, Somers V, et al. Tonic chemoreflex activation contributes to the elevated muscle sympathetic nerve activity in patients with chronic renal failure. J Hypertens. 2007;25(1):157–61.

    Article  PubMed  CAS  Google Scholar 

  7. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116(1):85–97.

    Article  PubMed  Google Scholar 

  8. Hausberg M, Grassi G. Mechanisms of sympathetic overactivity in patients with chronic renal failure: a role for chemoreflex activation? J Hypertens. 2007;25(1):47.

    Article  PubMed  CAS  Google Scholar 

  9. Chanda R, Fenves A. Hypertension in patients with chronic kidney disease. Curr Hypertens Rep. 2009;11(5):329–36.

    Article  PubMed  Google Scholar 

  10. Wright J, Hutchison A. Cardiovascular disease in patients with chronic kidney disease. Vasc Health Risk Manag. 2009;5:713–22.

    PubMed  Google Scholar 

  11. Burt V, Whelton P, Roccella E, Brown C, Cutler J, Higgins M, et al. Prevalence of hypertension in the US adult population: results from the Third National Health and Nutrition Examination Survey, 1988–1991. Hypertension. 1995;25(3):305–13.

    PubMed  CAS  Google Scholar 

  12. Kearney P, Whelton M, Reynolds K, Muntner P, Whelton P, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365(9455):217–23.

    PubMed  Google Scholar 

  13. Kosugi T, Nakagawa T, Kamath D, Johnson R. Uric acid and hypertension: an age-related relationship? J Hum Hypertens. 2009;23(2):75–6.

    Article  PubMed  CAS  Google Scholar 

  14. Yatsu K, Mizuki N, Hirawa N, Oka A, Itoh N, Yamane T, et al. High-resolution mapping for essential hypertension using microsatellite markers. Hypertension. 2007;49(3):446–52.

    Article  PubMed  CAS  Google Scholar 

  15. Koyama A, Igarashi M, Kobayashi M. Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases. Am J Kidney Dis. 1997;29(4):526–32.

    Article  PubMed  CAS  Google Scholar 

  16. D’Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis. 2000;36(2):227–37.

    Article  PubMed  Google Scholar 

  17. Yamamoto R, Nagasawa Y, Shoji T, Iwatani H, Hamano T, Kawada N, et al. Cigarette smoking and progression of IgA nephropathy. Am J Kidney Dis. 2010;56(2):313–24.

    Article  PubMed  CAS  Google Scholar 

  18. Yamamoto R, Nagasawa Y, Shoji T, Inoue K, Uehata T, Kaneko T, et al. A candidate gene approach to genetic prognostic factors of IgA nephropathy—a result of Polymorphism REsearch to DIstinguish genetic factors Contributing To progression of IgA Nephropathy (PREDICT-IgAN). Nephrol Dial Transplant. 2009;24(12):3686–94.

    Article  PubMed  CAS  Google Scholar 

  19. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982–92.

    Article  PubMed  CAS  Google Scholar 

  20. Yamada Y, Izawa H, Ichihara S, Takatsu F, Ishihara H, Hirayama H, et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. 2002;347(24):1916–23.

    Article  PubMed  CAS  Google Scholar 

  21. Walton K, Hsieh X, Gharavi N, Wang S, Wang G, Yeh M, et al. Receptors involved in the oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine-mediated synthesis of interleukin-8: a role for Toll-like receptor 4 and a glycosylphosphatidylinositol-anchored protein. J Biol Chem. 2003;278(32):29661–6.

    Article  PubMed  CAS  Google Scholar 

  22. Hasday JD, Bascom R, Costa JJ, Fitzgerald T, Dubin W. Bacterial endotoxin is an active component of cigarette smoke. Chest. 1999;115(3):829–35.

    Article  PubMed  CAS  Google Scholar 

  23. Michel O, Kips J, Duchateau J, Vertongen F, Robert L, Collet H, et al. Severity of asthma is related to endotoxin in house dust. Am J Respir Crit Care Med. 1996;154(6 Pt 1):1641–6.

    PubMed  CAS  Google Scholar 

  24. Wiedermann CJ, Kiechl S, Dunzendorfer S, Schratzberger P, Egger G, Oberhollenzer F, et al. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study. J Am Coll Cardiol. 1999;34(7):1975–81.

    Article  PubMed  CAS  Google Scholar 

  25. Raunio T, Knuuttila M, Karttunen R, Vainio O, Tervonen T. Serum sCD14, polymorphism of CD14(-260) and periodontal infection. Oral Dis. 2009;15(7):484–9.

    Article  PubMed  CAS  Google Scholar 

  26. Amar J, Ruidavets JB, Bal Dit Sollier C, Bongard V, Boccalon H, Chamontin B, et al. Soluble CD14 and aortic stiffness in a population-based study. J Hypertens. 2003;21(10):1869–77.

    Article  PubMed  CAS  Google Scholar 

  27. Pacheco E, Fonseca C, Montes C, Zabaleta J, Garca LF, Arias MA. CD14 gene promoter polymorphism in different clinical forms of tuberculosis. FEMS Immunol Med Microbiol. 2004;40(3):207–13.

    Article  PubMed  CAS  Google Scholar 

  28. Lin J, Yao YM, Yu Y, Chai JK, Huang ZH, Dong N, et al. Effects of CD14-159 C/T polymorphism on CD14 expression and the balance between proinflammatory and anti-inflammatory cytokines in whole blood culture. Shock. 2007;28(2):148–53.

    Article  PubMed  CAS  Google Scholar 

  29. Zee RY, Bates D, Ridker PM. A prospective evaluation of the CD14 and CD18 gene polymorphisms and risk of stroke. Stroke. 2002;33(4):892–5.

    Article  PubMed  CAS  Google Scholar 

  30. Risley P, Jerrard-Dunne P, Sitzer M, Buehler A, von Kegler S, Markus HS. Promoter polymorphism in the endotoxin receptor (CD14) is associated with increased carotid atherosclerosis only in smokers: the Carotid Atherosclerosis Progression Study (CAPS). Stroke. 2003;34(3):600–4.

    Article  PubMed  CAS  Google Scholar 

  31. Staessen J, Wang J, Ginocchio G, Petrov V, Saavedra A, Soubrier F, et al. The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk. J Hypertens. 1997;15(12):1579.

    Article  PubMed  CAS  Google Scholar 

  32. Shinoda H, Nishimoto K, Mochizuki T. Screening examination of Trichophyton tonsurans among Judo practitioners at the All Japan Inter High School Championships, Saga 2007. Nippon Ishinkin Gakkai Zasshi. 2008;49(4):305–9.

    Article  Google Scholar 

  33. Xie Y, Chen X, Nishi S, Narita I, Gejyo F. Relationship between tonsils and IgA nephropathy as well as indications of tonsillectomy. Kidney Int. 2004;65(4):1135–44.

    Article  PubMed  CAS  Google Scholar 

  34. Iio K, Nagasawa Y, Iwatani H, Yamamoto R, Horii A, Okuzaki D, et al. Microarray analysis of tonsils in immunoglobulin A nephropathy patients. Biochem Biophys Res Commun. 2010;393(4):565–70.

    Article  PubMed  CAS  Google Scholar 

  35. Suzuki S, Nakatomi Y, Sato H, Tsukada H, Arakawa M. Haemophilus parainfluenzae antigen and antibody in renal biopsy samples and serum of patients with IgA nephropathy. Lancet. 1994;343(8888):12–6.

    Article  PubMed  CAS  Google Scholar 

  36. Suzuki S, Fujieda S, Sunaga H, Sugimoto H, Yamamoto C, Kimura H, et al. Immune response of tonsillar lymphocytes to Haemophilus parainfluenzae in patients with IgA nephropathy. Clin Exp Immunol. 2000;119(2):328–32.

    Article  PubMed  CAS  Google Scholar 

  37. Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol. 2005;16(7):2088–97.

    Article  PubMed  CAS  Google Scholar 

  38. Appel GB, Waldman M. The IgA nephropathy treatment dilemma. Kidney Int. 2006;69(11):1939–44.

    Article  PubMed  CAS  Google Scholar 

  39. Port FK, Eknoyan G. The Dialysis Outcomes and Practice Patterns Study (DOPPS) and the Kidney Disease Outcomes Quality Initiative (K/DOQI): a cooperative initiative to improve outcomes for hemodialysis patients worldwide. Am J Kidney Dis. 2004;44(5 Suppl 2):1–6.

    Article  PubMed  Google Scholar 

  40. Isnard Bagnis C, Deray G, Baumelou A, Le Quintrec M, Vanherweghem JL. Herbs and the kidney. Am J Kidney Dis. 2004;44(1):1–11.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grant-in-aid for Young Scientists B (21790809), grant-in-aid for Scientific Research C (22590891), and grant from Osaka Kidney Bank (OK-3, 2009) and a travel grand from XLVII European Renal Association—European Dialysis Transplantation Association (ERA-EDTA) Congress in 2010.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Maki Shinzawa, Ryohei Yamamoto, Yasuyuki Nagasawa, Yoshitsugu Obi, Tomoko Namba, Harumi Kitamura, Hirotsugu Iwatani, Enyu Imai, Yoshitaka Isaka & Hiromi Rakugi

  2. Department of Kidney Disease and Hypertension, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka, Osaka, 558-8558, Japan

    Tatsuya Shoji, Tetsuya Kaneko, Noriyuki Okada & Yoshiharu Tsubakihara

  3. Division of Nephrology, Department of Internal Medicine, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai, Osaka, 591-8025, Japan

    Atsushi Yamauchi

Authors
  1. Maki Shinzawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryohei Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasuyuki Nagasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tatsuya Shoji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshitsugu Obi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoko Namba
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Harumi Kitamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tetsuya Kaneko
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Noriyuki Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hirotsugu Iwatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Atsushi Yamauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yoshiharu Tsubakihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Enyu Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yoshitaka Isaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Hiromi Rakugi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuyuki Nagasawa.

About this article

Cite this article

Shinzawa, M., Yamamoto, R., Nagasawa, Y. et al. Gene polymorphisms contributing to hypertension in immunoglobulin A nephropathy. Clin Exp Nephrol 16, 250–258 (2012). https://doi.org/10.1007/s10157-011-0553-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-011-0553-7

Keywords

Search

Navigation