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 (rs75492008, rs2594966, rs6442260 and rs8154), 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 rs2594966 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 rs6442260 and rs8154, PIK3CA rs1607237, and ULK1 rs4964879 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 rs75492008 and rs4964879 affect the correlation between C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) in MPA activity. Patients with rs8154 TT and rs1607237 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.
Keywords: ATG7 gene; microscopic polyangiitis (MPA); polymorphisms.
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