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An association between IL-10 promoter polymorphisms and diabetic nephropathy: a meta-analysis of case-control studies

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Abstract

Background

This study aimed to synthesize evidence on the association between IL-10 gene (−819 C/T, −1082 A/G, −592 A/C) polymorphisms and the risk of developing diabetic nephropathy.

Methods

A systematic literature search was done in health-related electronic databases. The search was limited to studies published in English until September 2017. We also checked the references of retrieved articles and relevant reviews for any additional studies. The methodological quality of the studies included in this review was assessed using the ‘Scales for Quality Assessment’. The I2 test was used to quantify between-study heterogeneity. A value of I2 > 50% indicated substantial heterogeneity. For the pooled analysis, summary odds ratio (OR) and its 95% confidence interval (CI) in random effect model were used.

Results

Eight case-control studies (1192 cases with diabetic nephropathy and 2399 controls) met the inclusion criteria. Three groups of people namely Africans, Asians and Caucasians were included in this review. There were significant protective effects of SNP -819 C/T in overall population (OR 0.32, 95% CI 0.26–0.4) and − 1082 A/G SNP in the Asian population (OR 0.64, 95% CI 0.47–0.86) on diabetic nephropathy in the recessive model. There was no significant effect of −592 A/C on diabetic nephropathy.

Conclusion

The findings suggest the protective effects of −1082A/G and -819G/A polymorphisms on the risk of developing diabetic nephropathy in type 2 diabetes mellitus, especially in the Asian population. Well- designed, prospective studies with sufficient number of participants are recommended to substantiate these findings.

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Abbreviations

AJOL :

African Journals online

CI :

confidence intervals

HWE :

Hardy-Weinberg equilibrium

IL :

interleukin

LILACS :

Latin American and Caribbean health sciences literature

MeSH :

medical subject heading

OR :

odds ratios

SNP :

single nucleotide polymorphism

T2DM :

type 2 diabetes mellitus

References

  1. Lyssenko V, Laakso M. Genetic screening for the risk of type 2 diabetes: worthless or valuable? Diabetes Care. 2013;36:120–6.

    Article  CAS  Google Scholar 

  2. Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683–765.

    Article  PubMed  CAS  Google Scholar 

  3. Cyktor JC, Turner J. Interleukin-10 and immunity against prokaryotic and eukaryotic intracellular pathogens. Infect Immun. 2011;79:2964–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Bijjiga E, Martino AT. Interleukin 10 (IL-10) regulatory cytokine and its clinical consequences. J Clin Cell Immunol. 2013;S1:007.

    Google Scholar 

  5. Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol. 2012;32:23–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Navarro-Gonzalez JF, Mora-Fernandez C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 2008;19:433–42.

    Article  PubMed  CAS  Google Scholar 

  7. Montazeri S, Nalliah S, Radhakrishnan AK. Is there a genetic variation association in the IL-10 and TNF alpha promoter gene with gestational diabetes mellitus? Hereditas. 2010;147:94–102.

    Article  PubMed  Google Scholar 

  8. Eskdale J, Kube D, Tesch H, Gallagher G. Mapping of the human IL10 gene and further characterization of the 5′ flanking sequence. Immunogenetics. 1997;46:120–8.

    Article  PubMed  CAS  Google Scholar 

  9. Karhukorpi J, Laitinen T, Karttunen R, Tiilikainen AS. The functionally important IL-10 promoter polymorphism (−1082G→A) is not a major genetic regulator in recurrent spontaneous abortions. Mol Hum Reprod. 2001;7:201–3.

    Article  PubMed  CAS  Google Scholar 

  10. Kilpinen S, Huhtala H, Hurme M. The combination of the interleukin-1α (IL-1α-889) genotype and the interleukin-10 (IL-10 ATA) haplotype is associated with increased interleukin-10 (IL-10) plasma levels in healthy individuals. Eur Cytokine Netw. 2002;13:66–71.

    PubMed  CAS  Google Scholar 

  11. Temple SE, Lim E, Cheong KY, Almeida CA, Price P, Ardlie KG, et al. Alleles carried at positions −819 and −592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae. Immunogenetics. 2003;55:629–32.

    Article  PubMed  CAS  Google Scholar 

  12. Seaquist ER, Goetz FC, Rich SS, Barbosa J. Familial clustering of diabetic kidney disease: evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med. 1998;320:1161–5.

    Article  Google Scholar 

  13. Rich SS. Genetics of diabetes and its complications. J Am Soc Nephrol. 2006;17:353–60.

    Article  PubMed  CAS  Google Scholar 

  14. Yaghini N, Mahmoodi M, Asadikaram GR, Hassanshahi GH, Khoramdelazad H, Arababadi M. Serum levels of interleukin 10 (IL-10) in patients with type 2 diabetic. Iran Red Crescent Med J. 2011;13:752.

    PubMed  PubMed Central  CAS  Google Scholar 

  15. Higgins JPT, Green S, ed. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration; 2011. Available from http://handbook.cochrane.org. Accessed 18 May 2018.

  16. Attia J, Thakkinstian A, D'Este C. Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol. 2003;56:297–303.

    Article  PubMed  Google Scholar 

  17. Thakkinstian A, McEvoy M, Minelli C, Gibson P, Hancox B, Duffy D, et al. Systematic review and meta-analysis of the association between{h}2-adrenoceptor polymorphisms and asthma: a HuGE review. Am J Epidemiol. 2005;162:201–11.

    Article  PubMed  Google Scholar 

  18. Guo SW, Thompson EA. 1992. Performing the exact test of hardy-Weinberg proportion for multiple alleles. Biometrics. 1992;48:361–72.

    Article  PubMed  CAS  Google Scholar 

  19. Lee YH. Meta- analysis of genetic association studies. Ann Lab Med. 2015;35:283–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Zintzaras E, Lau J. Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. J Clin Epidemiol. 2008;61:634–45.

    Article  PubMed  Google Scholar 

  21. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Babel N, Gabdrakhmanova L, Hammer MH, Schoenemann C, Skrypnikov V, Poliak N, et al. Predictive value of cytokine gene polymorphisms for the development of end-stage renal disease. J Nephrol. 2006;19:802–7.

    PubMed  CAS  Google Scholar 

  23. Ezzidi I, Mtiraoui N, Kacem M, Mallat SG, Mohamed MBH, Chaieb M, et al. Interleukin-10-592 C/A, -819C/T and -1082A/G promoter variants affect the susceptibility to nephropathy in Tunisian type 2 diabetes (T2DM) patients. Clin Endocrinol. 2009;70:401–7.

    Article  CAS  Google Scholar 

  24. Kung WJ, Lin CC, Liu SH, Chaung HC. Association of interleukin-10 polymorphisms with cytokines in type 2 diabetes nephropathy. Diabetes Technol Ther. 2010;12:809–13.

    Article  PubMed  CAS  Google Scholar 

  25. Erdogan M, Cetinkalp S, Ozgen AG, Saygili F, Berdeli A, Yilmaz C. Interleukin-10 (−1082G/a) gene polymorphism in patients with type 2 diabetes with and without nephropathy. Genet Test Mol Biomarkers. 2012;16:91–4.

    Article  PubMed  CAS  Google Scholar 

  26. Arababadi MK, Reza Mirzaei M, et al. Interleukin (IL)-10 gene polymorphisms are associated with type 2 diabetes with and without nephropathy: a study of patients from the southeast region of Iran. Inflammation. 2012;35:797–802.

    Article  PubMed  CAS  Google Scholar 

  27. Yin Q, Zhai Q, Wang D, Hai J, Cao M, Wang J, et al. Investigation on the association between inerleukin-10-592C/A, 819C/T and -1082A/G gene polymorphisms and development of diabetic nephropathy. Int J Clin Exp Pathol. 2015;8:15216–21.

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Ma DH, Xu QY, Liu Y, Zhai QQ, Guo MH. Association between interleukin-10 gene polymorphisms and susceptibility to diabetic nephropathy in a Chinese population. Genet Mol Res 2016;15(2). https://doi.org/10.4238/gmr.15027570.

  29. Mahmoud AA, Sheneef A, Sayed AA, Ezat MAW, Sabet EA. Association of interleukin-10 (−592 A/C) gene polymorphism with its level in type 2 diabetes mellitus with and without nephropathy. Mol Genet Med. 2016;10:1.

    Google Scholar 

  30. Wu HC, Ling H, Na SP, Xie RJ. The research on the relationship between the polymorphism of 1082A/G, anti-inflammatory interleukin-10 gene promoter with its effect of preventing ESRD patients from microinflammation and arteriosclerosis. Zhonghua Yi Xue Za Zhi. 2005;85:2076–80.

    PubMed  CAS  Google Scholar 

  31. Rodrigues KF, Pietrani NT, Sandrim VC, Vieira MAF, Fernandes AP, Bosco AA, et al. Association of a large panel of cytokine gene polymorphisms with complications and comorbidities in type 2 diabetes patients. J Diabeties Res. 2015; https://doi.org/10.1155/2015/605965.

  32. Tsiavou A, Hatziagelaki E, Chaidaroglou A, Manginas A, Koniavitou K, Degiannis D, et al. TNF-alpha, TGF-beta1, IL-10, IL-6, gene polymorphisms in latent autoimmune diabetic of adults (LADA) and type 2 diabetes mellitus. J Clin Immunol. 2004;24:591–9.

    Article  PubMed  CAS  Google Scholar 

  33. Chang YH, Huang CN, Wu CY, Shiau MY. Association of interleukin-10 −592 C/A and −819C/T polymorphisms with type 2 diabetes mellitus. Hum Immunol. 2005;66:1258–63.

    Article  PubMed  CAS  Google Scholar 

  34. Scarpelli D, Cardellini M, Andreozzi F, Laratta E, Hribal ML, Marini MA, et al. Variants of the interleukin-10 promoter gene are associated with obesity and insulin resistance but not type 2 diabetes in Caucasian Italian subjects. Diabetes. 2006;55:1529–33.

    Article  PubMed  CAS  Google Scholar 

  35. Saxena M, Agrawal CC, Bid HK, Banerjee M. An interleukin-10 gene promoter polymorphism (−592A/C) associated with type 2 diabetes: a north Indian study. Biochem Genet. 2012;50:549–59.

    Article  PubMed  CAS  Google Scholar 

  36. Mtiraoui N, Ezzidi I, Kacem M, Ben Hadj Mohamed M, Chaieb M, Haj Jilani AB, et al. Predictive value of interleukin-10 promoter genotypes and haplotypes in determining the susceptibility to nephropathy in type 2 diabetic patients. Diabetes Metab Res Rev. 2009;25:57–63.

    Article  PubMed  CAS  Google Scholar 

  37. World Health Organization (WHO). WHO expert committee on diabetes mellitus. WHO technical report series No. 646. Geneva: WHO; 1980.

    Google Scholar 

  38. American Diabeties Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2004;27:S5–S10.

    Article  Google Scholar 

  39. Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol. 2008;180:5771–7.

    Article  PubMed  CAS  Google Scholar 

  40. Zhang F, Yang Y, Lei H, Qiu J, Wang Y, Hu D, et al. A meta-analysis about the association between −1082 G/A and -819 C/T polymorphisms of IL-10 gene and risk of type 2 diabetes. Hum Immunol. 2013;74:618–26.

    Article  PubMed  CAS  Google Scholar 

  41. Mysliwska J, Zorena K, Semetkowska-Jurkiewicz E, Rachon D, Suchanek H, Mysliwski A. High levels of circulating interleukin-10 in diabetic nephropathy patients. Eur Cytokine Netw. 2005;16:117–22.

    PubMed  CAS  Google Scholar 

  42. Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH. Diabetic nephropathy is associated with low-grade inflammation in type diabetic patients. Diabetologia. 2003;46:1402–7.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors are grateful to the participants and researchers of the primary studies included in this analysis, and to the two anonymous reviewers and the editor for providing the comments and inputs to improve the quality of manuscript. We thank the International Medical University (IMU) in Kuala Lumpur of Malaysia for allowing us to perform this study.

Author information

Author notes

  1. Norah Htet Htet and Arun Kumar Basavaraj contributed equally to this work.

Authors and Affiliations

  1. Institute for Research, Development and Innovation (IRDI), International Medical University, Kuala Lumpur, Malaysia

    Cho Naing

  2. Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia

    Cho Naing

  3. School of Medicine, International Medical University, Kuala Lumpur, Malaysia

    Norah Htet Htet, Arun Kumar Basavaraj & Sivalingam Nalliah

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  1. Cho Naing
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  2. Norah Htet Htet
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Contributions

SN: conceptualized and coordinated the study; CN, NHH, AKB: designed; CN, NHH: extracted data; AKB: checked data accuracy; CN, NHH, AKB: assessed quality of studies; CN, NHH: analyzed; SN, CN, AKB, NHH: interpreted; CN: wrote the first draft; CN, NHH, AKB, SN: revised the manuscript; All authors approved the final version of the revised manuscript.

Corresponding author

Correspondence to Cho Naing.

Ethics declarations

Ethics approval and consent to participate

Ethics approval and consent were waived by the Joint Research and Ethics Committee at the International Medical University in Kula Lumpur of Malaysia as this study was exclusively performed with the published data.

Consent for publication

Not applicable.

Competing interest

The authors declare that they have no competing interests.

Electronic supplementary material

Additional File 1

Scale for quality assessment of molecular association studies of diabetic nephropathy (DOC 51 kb)

Additional File 2

Leave-one- out met analysis with −1082 A/G (PDF 88 kb)

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Naing, C., Htet, N.H., Basavaraj, A.K. et al. An association between IL-10 promoter polymorphisms and diabetic nephropathy: a meta-analysis of case-control studies. J Diabetes Metab Disord 17, 333–343 (2018). https://doi.org/10.1007/s40200-018-0349-3

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  • DOI: https://doi.org/10.1007/s40200-018-0349-3

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