Related Experiment Video

Updated: May 12, 2026

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification
10:21

Primary Sjogren's Syndrome Associated with Lung Adenocarcinoma: Probing the Potential Common Pathogenic Mechanisms and Experimental Verification

Published on: September 20, 2024

Genetic burden across core genes of the PI3K-AKT-mTOR pathway is associated with susceptibility to microscopic

Lizhen Li1,2,3, Jing Yang1, Chao Xue4

  • 1Department of Nephrology, Hunan Clinical Research Center for Chronic Kidney Disease, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.

Frontiers in Immunology
|May 11, 2026
PubMed
Abstract

Insights

Genetic variations in the PI3K-AKT-mTOR pathway increase microscopic polyangiitis (MPA) risk, particularly in females. A higher genetic burden score correlates with MPA susceptibility, suggesting a threshold effect.

Area of Science:

  • Immunogenetics
  • Molecular Biology
  • Rheumatology

Background:

  • The PI3K-AKT-mTOR pathway is crucial for immune regulation and linked to autoimmune diseases.
  • Understanding genetic contributions to microscopic polyangiitis (MPA) is vital for disease insights.

Purpose of the Study:

  • To investigate the association between genetic variations in PI3K-AKT-mTOR pathway genes and MPA susceptibility.
  • To explore potential sex-specific effects and pathway-level genetic burden in MPA.

Main Methods:

  • A genetic association study was conducted in a Chinese cohort of MPA patients and controls.
  • Four single nucleotide polymorphisms (SNPs) in PIK3CA, AKT1, and MTOR were analyzed.
  • A cumulative genetic burden score was calculated, and logistic regression was used.

Main Results:

  • Increased genetic burden in the PI3K-AKT-mTOR pathway was linked to higher MPA susceptibility.
  • A threshold-dependent effect was observed, with stronger associations in females.
  • Pathway-level genetic burden correlated with MPO-ANCA positivity, and protective haplotypes were identified.

Conclusions:

  • Genetic variations in core PI3K-AKT-mTOR pathway genes may influence MPA susceptibility.
  • Potential sex-related trends warrant further investigation in larger cohorts.
  • These findings suggest a pathway-level genetic architecture contributing to MPA.
Keywords:
MPO-ANCAPI3K–AKT–mTOR pathwayautoimmune vasculitisgenetic burdenmicroscopic polyangiitissex differences

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...