We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

3′ untranslated region variants in DEFA5 gene associated with susceptibility to IgA nephropathy in the Chinese Han population

    Hongwei Peng

    *Author for correspondence: Tel.: +86 029 8889 5902;

    E-mail Address: jintb@nwu.edu.cn

    Renal Medicine, Hainan Wanning People's Hospital, Wanning, Hainan Province, 571500, China

    ,
    Pingyun Fan

    Renal Medicine, Hainan Wanning People's Hospital, Wanning, Hainan Province, 571500, China

    ,
    Yifen Hong

    Renal Medicine, Hainan Wanning People's Hospital, Wanning, Hainan Province, 571500, China

    ,
    Jing He

    Renal Medicine, Hainan Wanning People's Hospital, Wanning, Hainan Province, 571500, China

    ,
    Xiangxiu Zeng

    Renal Medicine, Hainan Wanning People's Hospital, Wanning, Hainan Province, 571500, China

    ,
    Fengguo Xu

    Renal Medicine, Hainan Wanning People's Hospital, Wanning, Hainan Province, 571500, China

    ,
    Yunxia Zhao

    Renal Medicine, Hainan Wanning People's Hospital, Wanning, Hainan Province, 571500, China

    &
    Tianbo Jin

    Key Laboratory of Resource Biology & Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, Shaanxi, 710000, China

    Provincial Key Laboratory of Biotechnology of Shaanxi Province, Northwest University, Xi'an, China

    Published Online:https://doi.org/10.2217/bmm-2022-0518

    Aim: To evaluate the association between single-nucleotide polymorphisms in the 3′ untranslated region of the DEFA5 gene and IgA nephropathy (IgAN) risk, the authors performed an association study in the Chinese Han population. Materials & methods: The authors recruited 426 IgAN patients and 498 controls. The MassARRAY platform (Agena Bioscience, Inc., CA, USA) was used to genotype single-nucleotide polymorphisms in DEFA5. Odds ratios and 95% CIs were calculated through logistic regression analysis. Results: The authors observed that rs12716641 significantly reduced IgAN risk in the allele (odds ratio: 0.77; p = 0.026) and genotype (odds ratio: 0.75; p = 0.039) models. Stratification analysis revealed that several genotypes of rs12716641 played a protective role against IgAN. Conclusion: The authors' results revealed that single-nucleotide polymorphisms in the 3′ untranslated region of DEFA5 were associated with IgAN risk.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Berger J, Hinglais N. Intercapillary deposits of IgA–IgG. J. Urol. Nephrol. (Paris) 74(9), 694–695 (1968).
    • 2. Fabiano RC, Pinheiro SV, Simões ESaC. Immunoglobulin A nephropathy: a pathophysiology view. Inflamm. Res. 65(10), 757–770 (2016).
    • 3. Shima Y, Nakanishi K, Yoshikawa N. Non-immunosuppressive therapies for childhood IgA nephropathy. Pediatr. Nephrol. 36(10), 3057–3065 (2021).
    • 4. Kiryluk K, Li Y, Sanna-Cherchi S et al. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLOS Genet. 8(6), e1002765 (2012).
    • 5. Kiryluk K, Li Y. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat. Genet. 46(11), 1187–1196 (2014).
    • 6. Li M, Foo JN, Wang JQ et al. Identification of new susceptibility loci for IgA nephropathy in Han Chinese. Nat. Commun. 6, 7270 (2015). •• Largest study on IgAN in the Han Chinese population to date, analyzing a total of 8313 IgAN cases and 19,680 controls; discovering three new loci at 11p11.2, 8q22.3 and 3q27.3; significantly expanding our understanding of the genetic basis of IgAN susceptibility.
    • 7. Wilson SS, Wiens ME, Smith JG. Antiviral mechanisms of human defensins. J. Mol. Biol. 425(24), 4965–4980 (2013).
    • 8. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1(2), 113–118 (2000).
    • 9. Dugan AS, Maginnis MS, Jordan JA et al. Human α-defensins inhibit BK virus infection by aggregating virions and blocking binding to host cells. J. Biol. Chem. 283(45), 31125–31132 (2008).
    • 10. de Leeuw E, Burks SR, Li X, Kao JPY, Lu W. Structure-dependent functional properties of human defensin 5. FEBS Lett. 581(3), 515–520 (2007).
    • 11. Feng S, Zhong Z, Fan J, Li X, Shi D, Jiang L. Upregulated expression of intestinal antimicrobial peptide HD5 associated with renal function in IgA nephropathy. Dis. Markers 2020, 2078279 (2020). •• Found that elevated serum HD5 at the time of renal biopsy was associated with poor renal outcomes in IgAN patients and that HD5 rather than HD6 was probably associated with renal function in IgAN patients.
    • 12. Ferguson LR, Browning BL, Huebner C et al. Single-nucleotide polymorphisms in human Paneth cell defensin A5 may confer susceptibility to inflammatory bowel disease in a New Zealand Caucasian population. Dig. Liv. Dis. 40(9), 723–730 (2008).
    • 13. Feng Y, Su Y, Ma C et al. 3′UTR variants of TNS3, PHLDB1, NTN4, and GNG2 genes are associated with IgA nephropathy risk in Chinese Han population. Int. Immunopharmacol. 71, 295–300 (2019).
    • 14. Sabatino AD, Miceli E, Dhaliwal W et al. Distribution, proliferation, and function of Paneth cells in uncomplicated and complicated adult celiac disease. Am. J. Clin. Pathol. 130(1), 34–42 (2008).
    • 15. Tenge VR, Gounder AP, Wiens ME, Wuyuan L, Smith JG. Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition. PLoS Pathog. 10(9), e1004360 (2014).
    • 16. Ayabe T, Ashida T, Kohgo Y, Kono T. The role of Paneth cells and their antimicrobial peptides in innate host defense. Trends Microbiol. 12(8), 394–398 (2004).
    • 17. Lehrer RI, Jung G, Ruchala P, Andre S, Gabius HJ, Lu W. Multivalent binding of carbohydrates by the human alpha-defensin, HD5. J. Immunol. 183(1), 480–490 (2009).
    • 18. Bevins CL. Paneth cell defensins: key effector molecules of innate immunity. Biochem. Soc. Trans. 34(Pt 2), 263–266 (2006).
    • 19. Salzman NH, Ghosh D, Huttner KM, Paterson Y, Bevins CL. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422(6931), 522–526 (2003).
    • 20. Spencer JD, Hains DS, Porter E et al. Human alpha defensin 5 expression in the human kidney and urinary tract. PLOS ONE 7(2), e31712 (2012). • Found that HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney and that with infection, HD5 expression increases in the kidney and levels become detectable in the urine.
    • 21. Qi YY, Zhou XJ, Cheng FJ et al. DEFA gene variants associated with IgA nephropathy in a Chinese population. Genes Immun. 16(3), 231–237 (2015).