Functional genomics research of NPEPPS gene in the pathogenesis of ankylosing spondylitis
TONG Xiaojun1, LI Chenlu2, WANG Guofen1, ZHU Xiaochun2, WANG Xiaobing2
1.Department of Rheumatology, Taizhou Central Hospital, Affiliated Hospital of Taizhou College, Taizhou 318000, China; 2.Department of Rheumatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
TONG Xiaojun,LI Chenlu,WANG Guofen, et al. Functional genomics research of NPEPPS gene in the pathogenesis of ankylosing spondylitis[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2021, 51(3): 181-186,191.
Abstract：Objective: To investigate whether single nucleotide polymorphisms (SNPs) of NPEPPS gene can regulate the expression of NPEPPS gene and the pathogenesis of ankylosing spondylitis. Methods: Peripheral blood mononuclear cells (PBMC) from 54 patients with AS and 78 healthy control were collected from the Department of Rheumatology, the First Affiliated Hospital of Wenzhou Medical University. DNA and RNA were extracted, and Illumina platform was used for SNP microarray gene typing and RNA sequencing. The SNPs of our chromosome region containing NPEPPS were extracted by PLINK, the missing genotype was supplemented by IMPUTE2, and the genotype of the immune chip was calculated by PLINK. The reads obtained from RNA sequencing was compared to the human genome, and the read count of each gene was generated. The expression levels of different transcripts were calculated according to the reference transcriptome. Intergroup comparisons were made with DESeq2, and regression analysis was conducted with genotypes. Results: The expression of NPEPPS in both homozygous and heterozygous alleles of SNP rs9901869 was higher in AS patients than in the healthy control but the two groups showed no statistical difference (P>0.05); The expression levels of different transcripts were different in AS and healthy controls, among which the expression levels of TCONS_00206150, TCONS_00206153 and TCONS_00206137 were significantly different (P<0.05); the expression levels of NPEPSS genes and their transcripts corresponding to different SNP rs9901869 genotypes were different, with the expression levels of some transcripts showing statistical significance (P<0.05); the expression of NPEPPS gene and its transcript was significantly different due to different genotype of SNP rs180677251 near SNP rs9901869 (P<0.05). Conclusion: This study has revealed that the polymorphism of NPEPPS gene locus affects the expression level of NPEPPS, which may be correlated with the development of AS.
