3′ untranslated region variants in DEFA5 gene associated with susceptibility to IgA nephropathy in the Chinese Han population
Abstract
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. . Intercapillary deposits of IgA–IgG. J. Urol. Nephrol. (Paris) 74(9), 694–695 (1968).
- 2. . Immunoglobulin A nephropathy: a pathophysiology view. Inflamm. Res. 65(10), 757–770 (2016).
- 3. . Non-immunosuppressive therapies for childhood IgA nephropathy. Pediatr. Nephrol. 36(10), 3057–3065 (2021).
- 4. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis. PLOS Genet. 8(6), e1002765 (2012).
- 5. . Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat. Genet. 46(11), 1187–1196 (2014).
- 6. 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. . Antiviral mechanisms of human defensins. J. Mol. Biol. 425(24), 4965–4980 (2013).
- 8. . Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat. Immunol. 1(2), 113–118 (2000).
- 9. 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. . Structure-dependent functional properties of human defensin 5. FEBS Lett. 581(3), 515–520 (2007).
- 11. . 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. 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. 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. Distribution, proliferation, and function of Paneth cells in uncomplicated and complicated adult celiac disease. Am. J. Clin. Pathol. 130(1), 34–42 (2008).
- 15. . Delineation of interfaces on human alpha-defensins critical for human adenovirus and human papillomavirus inhibition. PLoS Pathog. 10(9), e1004360 (2014).
- 16. . The role of Paneth cells and their antimicrobial peptides in innate host defense. Trends Microbiol. 12(8), 394–398 (2004).
- 17. . Multivalent binding of carbohydrates by the human alpha-defensin, HD5. J. Immunol. 183(1), 480–490 (2009).
- 18. . Paneth cell defensins: key effector molecules of innate immunity. Biochem. Soc. Trans. 34(Pt 2), 263–266 (2006).
- 19. . Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422(6931), 522–526 (2003).
- 20. 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. DEFA gene variants associated with IgA nephropathy in a Chinese population. Genes Immun. 16(3), 231–237 (2015).