Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Association of MPPED2 gene variant rs10767873 with kidney function and risk of cardiovascular disease in patients with hypertension

Journal of Human Genetics volume 68, pages 393–398 (2023)Cite this article

Subjects

Abstract

Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline). By using multivariate linear regression analysis after adjustment for age, sex, traditional cardiovascular risk factors, and the use of antihypertensive drugs, as well as after correction for multiple comparison, patients with rs10767873T allele of the metallophosphoesterase domain containing 2 (MPPED2) gene were associated with higher level of eGFR (β = 0.041, p = 0.01) and lower levels of serum creatinine (β = −0.068, p = 0.001) and serum uric acid (β = −0.047, p = 0.02). But variant rs10767873 was not found to be associated with the risk of CKD, regardless of the types of antihypertensive drugs used. During a median 2.25-year follow-up, 152 CVD events were documented. Interestingly, patients with the rs10767873TT genotype had an increased risk of CVD events (hazard ratio, 1.74, 95% confidence interval, 1.11 to 2.73; p = 0.02) compared with patients carrying the wild-type genotype of rs10767873CC. In conclusion, our findings suggest variant rs10767873 of the MPPED2 gene is associated with kidney function and risk of CVD in Chinese hypertensive patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

References

  1. Wang Z, Chen Z, Zhang L, Wang X, Hao G, Zhang Z, et al. Status of hypertension in china: results from the China hypertension survey, 2012-2015. Circulation. 2018;137:2344–56.

    Article  PubMed  Google Scholar 

  2. Judd E, Calhoun DA. Management of hypertension in CKD: beyond the guidelines. Adv Chronic Kidney Dis. 2015;22:116–22.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wang S, Chen R, Liu Q, Shu Z, Zhan S, Li L. Prevalence, awareness and treatment of chronic kidney disease among middle-aged and elderly: The China Health and Retirement Longitudinal Study. Nephrology. 2015;20:474–84.

    Article  CAS  PubMed  Google Scholar 

  4. Wang F, Yang C, Long J, Zhao X, Tang W, Zhang D, et al. Executive summary for the 2015 Annual Data Report of the China Kidney Disease Network (CK-NET). Kidney Int. 2019;95:501–5.

    Article  PubMed  Google Scholar 

  5. Zhang J, Thio CHL, Gansevoort RT, Snieder H. Familial aggregation of CKD and heritability of kidney biomarkers in the general population: the lifelines cohort study. Am J Kidney Dis. 2021;77:869–78.

    Article  CAS  PubMed  Google Scholar 

  6. Stevens PE, Levin A. Kidney disease: improving global outcomes chronic kidney disease guideline development work group members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158:825–30.

    Article  PubMed  Google Scholar 

  7. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382:339–52.

    Article  PubMed  Google Scholar 

  8. Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet. 2017;389:1238–52.

    Article  PubMed  Google Scholar 

  9. Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, et al. Genetic loci influencing kidney function and chronic kidney disease. Nat Genet. 2010;42:373–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. O’Seaghdha CM, Fox CS. Genome-wide association studies of chronic kidney disease: what have we learned? Nat Rev Nephrol. 2011;8:89–99.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Okada Y, Sim X, Go MJ, Wu JY, Gu D, Takeuchi F, et al. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. Nat Genet. 2012;44:904–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pattaro C, Teumer A, Gorski M, Chu AY, Li M, Mijatovic V, et al. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nat Commun. 2016;7:10023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pugh D, Gallacher PJ, Dhaun N. Management of hypertension in chronic kidney disease. Drugs. 2019;79:365–79.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rysz J, Franczyk B, Rysz-Górzyńska M, Gluba-Brzózka A. Pharmacogenomics of hypertension treatment. Int J Mol Sci. 2020;21:4709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhao JV, Schooling CM. Using Mendelian randomization study to assess the renal effects of antihypertensive drugs. BMC Med. 2021;19:79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tonelli M, Muntner P, Lloyd A, Manns BJ, James MT, Klarenbach S, et al. Using proteinuria and estimated glomerular filtration rate to classify risk in patients with chronic kidney disease: a cohort study. Ann Intern Med. 2011;154:12–21.

    Article  PubMed  Google Scholar 

  17. Wen CP, Cheng TY, Tsai MK, Chang YC, Chan HT, Tsai SP, et al. All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan. Lancet. 2008;371:2173–82.

    Article  PubMed  Google Scholar 

  18. Chen Y, Yang Y, Zhong Y, Li J, Kong T, Zhang S, et al. Genetic risk of hyperuricemia in hypertensive patients associated with antihypertensive drug therapy: a longitudinal study. Clin Genet. 2022;101:411–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Smeland OB, Frei O, Shadrin A, O’Connell K, Fan CC, Bahrami S, et al. Discovery of shared genomic loci using the conditional false discovery rate approach. Hum Genet. 2020;139:85–94.

    Article  CAS  PubMed  Google Scholar 

  20. Gauderman WJ, Morrison JM. Quanto 1.1: a computer program for power and sample size calculations for genetic epidemiology studies. http://hydra.usc.edu/gxe. 2006

  21. Tyagi R, Shenoy AR, Visweswariah SS. Characterization of an evolutionarily conserved metallophosphoesterase that is expressed in the fetal brain and associated with the WAGR syndrome. J Biol Chem. 2009;284:5217–28.

    Article  CAS  PubMed  Google Scholar 

  22. Schwartz F, Eisenman R, Knoll J, Gessler M, Bruns G. cDNA sequence, genomic organization, and evolutionary conservation of a novel gene from the WAGR region. Genomics. 1995;29:526–32.

    Article  CAS  PubMed  Google Scholar 

  23. Shen L, Liu L, Ge L, Xie L, Liu S, Sang L, et al. miR-448 downregulates MPPED2 to promote cancer proliferation and inhibit apoptosis in oral squamous cell carcinoma. Exp Ther Med. 2016;12:2747–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pattaro C, Köttgen A, Teumer A, Garnaas M, Böger CA, Fuchsberger C, et al. Genome-wide association and functional follow-up reveals new loci for kidney function. PLoS Genet. 2012;8:e1002584.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Matsushita K, Coresh J, Sang Y, Chalmers J, Fox C, Guallar E, et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3:514–25.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ataklte F, Song RJ, Upadhyay A, Musa Yola I, Vasan RS, Xanthakis V. Association of mildly reduced kidney function with cardiovascular disease: the Framingham Heart Study. J Am Heart Assoc. 2021;10:e020301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Leong DP, Joseph PG, McKee M, Anand SS, Teo KK, Schwalm JD, et al. Reducing the global burden of cardiovascular disease, part 2: prevention and treatment of cardiovascular disease. Circ Res. 2017;121:695–710.

    Article  CAS  PubMed  Google Scholar 

  28. De Bacquer D, Ueda P, Reiner Ž, De Sutter J, De Smedt D, Lovic D, et al. Prediction of recurrent event in patients with coronary heart disease: the EUROASPIRE Risk Model. Eur J Prev Cardiol. 2022;29:328–39.

    Article  PubMed  Google Scholar 

  29. Erdmann J, Kessler T, Munoz Venegas L, Schunkert H. A decade of genome-wide association studies for coronary artery disease: the challenges ahead. Cardiovasc Res. 2018;114:1241–57.

    CAS  PubMed  Google Scholar 

  30. Blake R, Raij L, Hernandez Schulman I. Renal protection: are all antihypertensive drugs comparable? Curr Hypertens Rep. 2007;9:373–9.

    Article  CAS  PubMed  Google Scholar 

  31. Ruggenenti P, Perna A, Mosconi L, Matalone M, Garini G, Salvadori M, et al. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997;349:1857–63.

    Article  Google Scholar 

  32. Bakris GL, Hart P, Ritz E. Beta blockers in the management of chronic kidney disease. Kidney Int. 2006;70:1905–13.

    Article  CAS  PubMed  Google Scholar 

  33. Delanaye P, Cavalier E, Cristol JP, Delanghe JR. Calibration and precision of serum creatinine and plasma cystatin C measurement: impact on the estimation of glomerular filtration rate. J Nephrol. 2014;27:467–75.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank doctors and nurses at Benxi Railway Hospital, Liaoning, and Hongxinglong Center Hospital, Heilongjiang, China for data collection.

Funding

This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-1-I2M-011), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period from the Ministry of Science and Technology, China (2011BAI11B04), and the Scientific and Technological Projects of Xiamen City (2100004).

Author information

Author notes

  1. These authors contributed equally: Yixuan Zhong, Yiyi Wu, Yunyun Yang.

Authors and Affiliations

  1. National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100037, China

    Yixuan Zhong, Yiyi Wu, Yu Chen, Rutai Hui & Weili Zhang

  2. The First Affiliated Hospital of Anhui University of Science and Technology (The First People’s Hospital of Huainan City), Huainan, 232000, Anhui, China

    Yiyi Wu & Mei Zhang

  3. The First Affiliated Hospital of Xiamen University; Clinical laboratory; Xiamen Key Laboratory of Genetic Testing, Xiamen, 361000, Fujian, China

    Yunyun Yang

  4. Central-China Branch of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Hospital, Zhengzhou, 450046, China

    Weili Zhang

Authors
  1. Yixuan Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yiyi Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yunyun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rutai Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Weili Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WZ contributed to the conception and design of this work. YZ, YW, and YY contributed to the analysis and interpretation of data for the work. YW and YZ drafted the manuscript. YC, RH and MZ contributed to acquisition and interpretation of data. WZ and MZ critically revised the manuscript. All authors gave final approval and agree to be accountable for all aspects of the work ensuring integrity and accuracy.

Corresponding authors

Correspondence to Mei Zhang or Weili Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhong, Y., Wu, Y., Yang, Y. et al. Association of MPPED2 gene variant rs10767873 with kidney function and risk of cardiovascular disease in patients with hypertension. J Hum Genet 68, 393–398 (2023). https://doi.org/10.1038/s10038-022-01118-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s10038-022-01118-w

Search

Advanced search

Quick links