Background The association between major histocompatibility complex (MHC) regions and systemic lupus erythematosus (SLE) has been widely established.
Methods To refined the most significant independent MHC loci with SLE susceptibility and clinical manifestations in Chinese Han population, we conducted stepwise conditional analysis 7,342 SLE cases and 7,185 control subjects of Chinese Han population based on the genotyped MHC region in Genome-wide association studies data by the Han-MHC reference panel in 1000 Genomes Project phase 3. Meta-analysis was performed in part of those independent loci with other ethnic populations from published studies. The correlation between the independent variants and SLE clinical feature was assessed by chi-square test.
Results A total of 1427 HLA variants significantly associated with SLE were identified(P<5×10–8): amino acid residue at position 233 in HLA-DRB1 (P=2.99×10–4, OR 0.81), HLA-DRB1*15:01(P=2.46×10–5, OR 1.37) and rs3135393(P=1.74×10–4, OR 0.71) contributing the strongest signal. Stepwise conditional analysis revealed 20 independent variants including 15 novel loci with most strongly statistically association signal.
Meta-analysis of different ethnic groups confirmed 3 alleles shown consistent role to disease predisposed effects in multiple races and HLA-DQB1*03:01 present slightly different in different race. In a sub-phenotype comparative analysis, a link between 7 alleles, 5 amino acid residue and 3 SNP of HLA independent variant were detected strongly signal with different clinical manifestations of SLE.
Conclusions Our study emphasized the genetic value of the MHC region in the predisposition and its clinical feature of SLE in Chinese Han population. This funding provided a new perspective for early diagnosis, prevention, intervention among autoimmune diseases.
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