FOXP3 gene polymorphisms increase the risk of systemic lupus erythematosus in a Han Chinese population

Ann Med. 2024 Dec;56(1):2363937. doi: 10.1080/07853890.2024.2363937. Epub 2024 Jun 7.

Abstract

Background: FOXP3 is a transcription factor that regulates the development and function of Treg, playing an essential role in preventing autoimmune diseases. Variation in FOXP3 can impair the function of Treg cells, thus destroying their inhibitory capacity and leading to autoimmune diseases. This paper investigated whether the three SNPs in the FOXP3 gene (-3279 C/A, -924 A/G and -6054 del/ATT) are associated with systemic lupus erythematosus (SLE) susceptibility in the Han Chinese population.

Materials and methods: The study cohort comprised 122 SLE patients and 268 healthy controls. Genotyping was performed by polymerase chain reaction sequence-specific primer (PCR-SSP). Furthermore, we examined the potential clinical manifestations associated with FOXP3 polymorphisms in SLE patients.

Results: The results showed that the -3279 (C > A) was significantly associated with the SLE risk in a homozygote (OR = 3.24, 95% CI = 1.23-8.52, p = .013, AA vs. CC), dominant (OR = 1.68, 95% CI = 1.07-2.65, p = .025, AC + AA vs. CC), recessive (OR = 2.90, 95% CI = 1.12-7.55, p = .023, AA vs. AC + CC) and allelic (OR = 1.72, 95% CI = 1.18-2.53, p = .005, A vs. C) models. In addition, -924 (A > G) was positively associated with SLE risk in the heterozygote (OR = 1.66, 95% CI = 1.04-2.66, p = .033, AG vs. AA) and dominant (OR = 1.59, 95% CI = 1.01-2.49, p = .042, AG + GG vs. AA) models, whereas -6054 (del > ATT) was not associated with SLE. Moreover, the immunological index analysis suggested that decreased complement C4 occurred more frequently in SLE patients carrying the minor allele (A) -3279 (C > A) than those not (p = .005).

Conclusions: We demonstrated that -3279 (C > A) and -924 (A > G) were associated with an increased risk of SLE and the immunological index, indicating that the FOXP3 variation is potentially related to the occurrence and development of SLE.

Keywords: FOXP3; immune index; polymorphism; systemic lupus erythematosus.

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • China / epidemiology
  • East Asian People
  • Female
  • Forkhead Transcription Factors* / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Lupus Erythematosus, Systemic* / genetics
  • Lupus Erythematosus, Systemic* / immunology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Young Adult

Substances

  • Forkhead Transcription Factors
  • FOXP3 protein, human

Grants and funding

This study received financial support from the National Natural Science Foundation of China (NSFC) under Grant Numbers 81901663 and 82271851. Additionally, it was supported by Young Backbone Teachers Training Program of Henan Province under Grant Number 2023GGJS048 and Key Project of Medical Science and Technology Research Program of Henan Province (SBGJ202002098).