PeerJ (Nov 2021)

Gene polymorphisms in ULK1 and PIK3CA are associated with the risk of microscopic polyangiitis in the Guangxi Zhuang Autonomous Region in China

  • Yan Zhu,
  • Jinlan Rao,
  • Jingsi Wei,
  • Liu Liu,
  • Shanshan Huang,
  • Jingjing Lan,
  • Chao Xue,
  • Wei Li

DOI
https://doi.org/10.7717/peerj.12377
Journal volume & issue
Vol. 9
p. e12377

Abstract

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Background Microscopic polyangiitis (MPA) is a systemic autoimmune disease characterized by inflammation of small- and medium-sized blood vessels. Autophagy-related protein polymorphisms are involved in autoimmune disease. The aim of this study was to evaluate the effects of single-nucleotide polymorphisms (SNPs) in the ULK1 and PIK3CA genes on the risk of MPA. Method A total of 208 patients with MPA and 211 controls in the Guangxi Zhuang Autonomous Region were recruited and analyzed. The SNPs selected were detected by polymerase chain reaction and high-throughput sequencing. The differences in allele and genotype frequency, various genetic models, and stratification analyses were evaluated, haplotype evaluation was performed after linkage disequilibrium analysis, and the interaction between gene alleles was analyzed. Results A statistically significant difference was detected in the genotypic distribution of two SNPs between the two groups: ULK1 rs4964879 (p = 0.019) and PIK3CA rs1607237 (p = 0.002). The results of the genetic models revealed that ULK1 rs4964879 and rs9481 were statistically significantly associated with an increased risk of MPA, whereas PIK3CA rs1607237 was associated with a reduced risk. The association between SNPs and MPA risk was affected by age, sex, and ethnicity. The ULK1 haplotype (G-T-A-C-G-A) and PIK3CA haplotype (T-G) were associated with a reduced risk of MPA, while the PIK3CA haplotype (C-G) was associated with an increased risk. Conclusion In this study, polymorphisms in the autophagy-related genes ULK1 and PIK3CA and their association with MPA were examined. The results showed that the polymorphisms in ULK1 (rs4964879 and rs9481) and PIK3CA (rs1607237) were significantly associated with MPA risk in the Guangxi population. However, the molecular mechanisms are still unclear; basic science research and studies with larger samples are needed to confirm our conclusions and explore the underlying mechanisms.

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