A
Study on the Association of HLA-DR Alleles,gene sequence and patients with
Systemic Lupus Erythematosus in Chinese Children
LI
Caifeng HE Xiaohu JIANG
Zaifang et al
Objective: To study the correlation between
HLA- DR alleles and systemic lupus erythematosus(SLE) in Chinese children and
to find the influence of HLA gene with clinical phenomenon by sequence
analysis.Methods: HLA- DR
alleles were tested in 53 patients with SLE (lupus nephritis 15, lupus
encephalopathy 7, lupus nephritis and lupus encephalopathy 10, and 21 without
either lupus nephritis or lupus encephalopathy) and 78 normal controls by
Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP).The gene
sequence of HLA-DRB1*15 in 35 cases of SLE with HLA-DRB1*15 was tested by
Polymerase Chain Reaction - Single Strand Conformational Polymorphism(PCR-SSCP)
and PCR productions sequencing to discover gene mutation.
Results: The frequency of HLA-DRB1*15,
DRB1*03 in SLE group was much higher than that in control group with
significant statistical difference (PC0.05), the RR were 4.5238 and
5.4146 respectively. The frequency of HLA-DRB1*04 in SLE group was much lower
than that in control group with significant statistical difference
(PC0.05). Clinical date showed that patients with DRB1*03 much more
easily complicated with lupus nephritis, whereas the patients with DRB1*15 had
all kinds of the clinical manifestations.The sequence analysis results showed
that 6 cases had C→G replacement mutation in 123th nucleotide resulting in D→E
replacement (aspartic acid to glutamic acid) in 41th amino acid. Clinical data
showed that 4/6 cases with mutation had both lupus nephritis and CNS lupus,
whereas 4/29 cases without mutation didn’t complicate with either lupus nephritis or lupus
encephalopathy. Conclusion: These
findings suggested that HLA-DRB1*15, HLA-DRB1*03 were susceptible genes in SLE,
and HLA-DRB1*04 was protective gene. DRB1*03 mainly associated with lupus
nephritis and DRB1*15 was associated with all kind of clinical types.
HLA-DRB1*15 gene mutation and replacement of amino acid were correlated with
the severity of SLE. We presumed that the clinical phenotypes of severe
patients might be due to the replacement of amino acid, which might result in
changes of the construction of HLA molecule and influence their functions.We
inferred that the HLA structural changes might influence the clinical types.
[Key
Words] SLE; HLA Alleles;
Predisposing Gene;Gene Mutation