Microscopic polyangiitis (MPA) is a type of antineutrophil cytoplasmic antibody (ANCA)-related vasculitis. Autophagy-related gene 7 (ATG7) protects against complicated disorder states in model organisms, but the way ATG7 dysfunction contributes to MPA remains elusive. This investigation assessed the impacts of ATG7 single-nucleotide polymorphisms (SNPs) on microscopic polyangiitis (MPA) in China. A total of 211 controls and 214 MPA patients were recruited and analyzed. Polymerase chain reaction (PCR) and high-throughput sequencing were adopted to detect the ATG7 SNPs ( and ), and stratification analysis, different genetic models and differences in allele and genotype frequencies were evaluated. Haplotype evaluation was performed after linkage disequilibrium (LD) analyses, and interactions between alleles were assessed. Generalized multifactor dimensionality reduction (GMDR) was adopted to analyze SNP-SNP interactions among the four ATG7 SNPs and phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and unc-nc-like autophagy activating kinase 1 (ULK1) SNPs previously studied by our team. Relationships between ATG7 polymorphisms, disease activity biomarkers and therapeutic effects in MPA were analyzed. Sex stratification analysis of the GG genotype with codominant and recessive models showed OR=3.42, 95% CI [1.19-9.80], P=0.041 and OR=3.31, 95% CI [1.23-8.90], P=0.012, respectively. Haplotype G-G-C-T was related to an increased MPA risk (OR=1.5, 95% CI [0.999-2.266], P=0.029). Permutation testing of GMDR suggested that ATG7 and , PIK3CA , and ULK1 might interact with each other in MPA development (P<0.05). Among 214 MPA patients, 79 available complete follow-up clinical datasets were gathered from September 2009 to October 2020, showing that and affect the correlation between C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) in MPA activity. Patients with TT and CC genotypes had better clinical treatment effects (P<0.05). Gene polymorphisms may be related to MPA in China, exhibiting correlation with MPA activity indicators, treatment and prognosis.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9641429PMC

Publication Analysis

Top Keywords

microscopic polyangiitis
12
polyangiitis mpa
8
atg7 snps
8
stratification analysis
8
mpa
7
atg7
7
association atg7
4
atg7 gene
4
gene polymorphisms
4
polymorphisms microscopic
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!