No abstract

No abstract

Microscopic polyangiitis (MPA) is an autoimmune disease, characterized by ANCA in blood and necrotizing inflammation of small and medium-sized vessels, one of the three clinical phenotypes of ANCA-associated vasculitis (AAV). Autophagy has been confirmed to be involved in the pathogenesis of AAV. AKT1 is one of the autophagy-regulated proteins. Its single nucleotide polymorphisms (SNPs) are associated with multiple immune-related diseases, but there are rarely studies in AAV. The incidence rate of AAV has a notable geographic difference, and MPA is predominant in China. The aim of this study was to investigate the association between AKT1 SNP and MPA risk. Genotypes of 8 loci in AKT1 were evaluated by multiplex polymerase chain reaction (PCR) and high-throughput sequencing in 416 people, including 208 MPA patients and 208 healthy volunteers from Guangxi in China. Additionally, data of 387 healthy volunteers from China were obtained from the 1000Genomes Project on public database. Differences were observed between the loci (rs2498786, rs2494752, and rs5811155) genotypes in AKT1 and MPA risk (P = 7.0 × 10–4, P = 3.0 × 10–4, and P = 5.9 × 10–5, respectively). A negative association was detected in the Dominant model (P = 1.2 × 10–3, P = 2.0 × 10–4 and P = 3.6 × 10–5, respectively). A haplotype (G-G-T) was associated with MPA risk negatively (P = 7.0 × 10–4). This study suggests that alleles (rs2498786 G, rs2494752 G and rs5811155 insT) are protective factors for MPA and alleles (rs2494752 G and rs5811155 insT) for MPO-ANCA in patients with MPA. There is a haplotype (G-G-T), which is a protective factor for MPA. It suggests that the role of AKT1 in MPA/AAV needs further study to provide more intervention targets for MPA/AAV.

No abstract

Objectives To investigate the association of autophagy‐associated gene 10 (ATG10) gene polymorphisms (rs1864182 and rs1864183) with antineutrophil cytoplasmic autoantibody (ANCA)‐associated vasculitis (AAV) in Chinese Guangxi population. Methods The single nucleotide polymorphisms (SNPs) of ATG10 rs1864182 and rs1864183 in 395 participants (195 AAVs and 200 healthy controls) were genotyped. Generalized multiple dimensionality reduction (GMDR) was used to analyze the SNP‐SNP interactions among two SNPs of ATG10 gene and other SNPs of autophagy gene previously studied by our research team. Results In this study, we found that the two ATG10 SNPs were not associated with AAV risk in Chinese Guangxi population. However, there were statistically significant differences in the incidence of hemoptysis, hematuria, and proteinuria among the three genotypes of ATG10 rs1864182 and rs1864183 (p < 0.05). Moreover, permutation test of GMDR suggested that immunity‐related GTPase M(IRGM) rs4958847, autophagy‐associated gene 7 (ATG7) rs6442260, ATG7 rs2594966, ATG10 rs1864183, protein kinase B(AKT2) rs3730051, and AKT2 rs11552192 might interact with each other in the process of developing AAV (p < 0.05). Conclusions Our results indicated that there existed no association between ATG10 SNPs and AAV, and SNP‐SNP interactions among IRGM rs4958847, ATG7 rs6442260, ATG7 rs2594966, ATG10 rs1864183, AKT2 rs3730051, and AKT2 rs11552192 may confer AAV risk in the Chinese Guangxi population.