The regulation between risk loci single nucleotide polymorphism rs9268832 and susceptibility gene human leukocyte antigen DRB1 in systemic lupus erythematosus
10.3760/cma.j.cn141217-20221206-00495
- VernacularTitle:系统性红斑狼疮风险位点单核苷酸多态性rs9268832与易感基因人类白细胞抗原-DRB1表达调控的研究
- Author:
Jinli LIU
1
;
Tengfei XU
;
Quanzhen LI
Author Information
1. 山东大学附属威海市立医院检验科，威海 264200
- Keywords:
Lupus erythematosus, systemic;
Single nucleotide polymorphism;
Human leukocyte antigen;
Expression regulation
- From:
Chinese Journal of Rheumatology
2024;28(10):733-737
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the regulatory relationship between the loci single nucleotide polymorphism(SNP) rs9268832 and susceptibility gene human leukocyte antigen(HLA) DRB1 in systemic lupus erythematosus (SLE), and to enhance the understanding of genetic susceptibility to SLE.Methods:①A total of 223 out-and inpatients with SLE and 2 223 healthy controls were collected from Weihai Municipal Hospital from September 2017 to September 2019, and the SNP sites that might significantly associated with SLE were screened by genome-wide association study. ②Sequencing technology was used to genotype 100 out and -in patients with SLE and 100 healthy controls in Weihai Municipal Hospital from December 2019 to December 2020, the levels of anti-nuclear antibody and anti-double-stranded DNA antibody were detected by indirecte immunofluorescence and chemiluminescence immunoassay. Real-time quantitative PCR was used to determine HLA-DRB1 mRNA expression in peripheral blood mononuclear cells and B lymphocytes of 100 patients with SLE. ③One-way analysis of variance was used in this study, and SNK- q test or Tamhane′s T2 test were used for comparison between groups. Results:①A number of SNPs associated with SLE were identified by genome-wide association studies. Rs9268832, located in the HLA-DR region of susceptibility genes, was significantly associated with antinuclear antibodies. ②Of the 100 SLE patients, 41 had TT genotype of rs9268832, 32 had CT genotype, and 27 had CC genotype. In the 100 normal subjects, 10 had TT genotype of rs9268832, 59 had CT genotype, and 31 had CC genotype. The distribution frequency of T allele in SLE patients is higher than in normal people( χ2=27.58, P=0.020). ③Indirecy immunofluorescence and Chen iluminescence results showed that compared with CC genotype [antinuclear antibody (23.5±1.2)U/ml, anti-double-stranded DNA antibody (16.6±0.9)U/ml], CT genotype [antinuclear antibody (40.2±2.5)U/ml, anti-double-stranded DNA antibody (36.2±1.8)U/ml] were increased ( q=5.35, P=0.004; q=4.23, P=0.002), TT genotype [antinuclear antibody (56.3±3.1)U/ml, anti-double-stranded DNA antibody (52.5±2.9)U/ml] were increased ( q=8.21, P<0.001; q=7.59, P<0.001). PCR results showed that : compared with CC genotype [monocyte (402±8)×10 3, lymphocyte (462±7)×10 3], CT genotype [monocyte (572±11)×10 3, lymphocyte (470±8)×10 3] increased HLA-DRB1 mRNA expression ( q=1.11, P=0.030; q=1.03, P=0.040), TT genotype [monocytes (1 052±16)×10 3, lymphocytes (856±6)] increased HLA-DRB1 mRNA expression ( q=4.27, P=0.007; q=3.05, P=0.010). Conclusion:The T allele of SNP rs9268832 may be a risk locus for SLE, and there may be a regulatory relationship between different genotypes and the expression of susceptibility gene HLA-DRB1.
