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Updated: Sep 15, 2025

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Gene-Environment Interaction: Lessons From Complement-Mediated Kidney Disease.

Nattawat Klomjit1, Jing Miao2, Anuja Java3

  • 1Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, MN.

Seminars in Nephrology
|July 16, 2025
PubMed
Summary
This summary is machine-generated.

Complement dysregulation causes kidney diseases like atypical hemolytic uremic syndrome (aHUS). Genetic factors and environmental triggers interact, leading to incomplete penetrance and disease manifestation.

Keywords:
Complement-mediated TMAaHUScomplement mutationsenvironmental triggerspolymorphisms

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Area of Science:

  • Nephrology
  • Immunology
  • Genetics

Background:

  • Complement dysregulation underlies diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy.
  • Genetic variants and acquired factors like autoantibodies contribute to complement-mediated thrombotic microangiopathy (CM-TMA).
  • Incomplete penetrance, where genetic predisposition requires environmental triggers (infections, pregnancy, medications, etc.), is crucial for disease onset.

Purpose of the Study:

  • To review complement system activation and regulation.
  • To explore the role of complement in various kidney diseases.
  • To elucidate genetic drivers and environmental triggers of complement activation, using aHUS as a model.

Main Methods:

  • Literature review of complement system activation and regulation.
  • Analysis of genetic and environmental factors in complement-mediated kidney diseases.
  • Case study approach focusing on atypical hemolytic uremic syndrome (aHUS).

Main Results:

  • Complement activation is central to aHUS, C3 glomerulopathy, IgA nephropathy, lupus nephritis, ANCA-associated vasculitis, and membranous nephropathy.
  • Gene-environment interactions significantly influence disease development and presentation.
  • Genetic polymorphisms can disrupt the balance between complement activation and control.

Conclusions:

  • Understanding complement dysregulation is key to managing these kidney diseases.
  • Identifying genetic predispositions and environmental triggers is vital for predicting and preventing disease.
  • Further research into the complex interplay of genetics and environment in complementopathies is warranted.