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Abstract: PO1841

Associations of Genetic Variants Contributing to Gut Microbiota Composition in IgAN

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • He, Jiawei, Peking University First Hospital, Beijing, Beijing, China
  • Zhou, Xujie, Peking University First Hospital, Beijing, Beijing, China
  • Wang, Yanna, Peking University First Hospital, Beijing, Beijing, China
  • Liu, Lijun, Peking University First Hospital, Beijing, Beijing, China
  • Shi, Sufang, Peking University First Hospital, Beijing, Beijing, China
  • Lv, Jicheng, Peking University First Hospital, Beijing, Beijing, China
  • Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China
Background

Gut microbiota is observed to be associated with IgAN, as immune response in the gut is assumed to be one of the triggers of its development. And because the microbial composition is heritable, we hypothesize that genetic variants controlling gut microbiota composition may associate with susceptibility to IgAN or clinical phenotypes.

Methods

175 gut-microbiome-associated genetic variants were retrieved from GWAS Catalog. Genetic associations were examined in 1511 patients with IgAN and 4469 controls. Sub-phenotype associations and microbiome annotations were undertaken for better understanding how genes shaped phenotypes. Likely candidate microbes suggested in genetic associations were validated using 16s rDNA sequencing in 29 patients with IgAN and 20 controls.

Results

Nine genetic variants associated with susceptibility to IgAN (P values from 4.13×10-2 to 1.39×10-3). The rs1889714-AA/AG risk genotypes associated with higher serum levels of Gd-IgA1 (A). Other significant findings included the associations between rs148330122-CC risk genotype and early age of onset (B), rs6065904-AA/AG risk genotypes and worse kidney function (C), rs9363741-GG/GA risk genotypes and severer hematuria (D). Besides, rs1889714-AA/AG risk genotypes associated with decreased abundance of beneficial Dialister; whereas rs6065904-AA/AG and rs9363741-GG/GA risk genotypes associated with increased abundance of detrimental Erysipelotrichaceae and Lachnobacterium, respectively. 16S rDNA sequencing data validated the decreased Dialister (E), and a tendency of increased Erysipelotrichaceae and Lachnospiraceae abundance in faeces from IgAN (F/G).

Conclusion

Our results provided supporting evidence that gut microbiota in IgAN was affected by host genetics and shed light on candidate bacteria for future pathogenesis studies.

Funding

  • Government Support - Non-U.S.