| Systemic lupus erythematosus (SLE) is a complex autoimmune disorder which is characterized by autoantibody production, complement activation and immune-complex deposition, resulting in multiple organ systems damage.The clinical manifestations of SLE are complicated.Genetic and environmental factors are thought to contribute to the development of this disease. Asians seem to have higher disease prevalence and a higher rate of lupus nephritis.With the application of Genome-wide association study (GWAS), more and more SLE susceptibility genes/loci have been identified, Ethnic differences have been observed in susceptibility genes of SLE. Human leukocyte antigen-G(HLA-G) is a nonclassical HLA I antigen, It is one of molecules involved in immune toleranee through a variety of mechanisms involved in immune response and maintenance. Studies have shown that there are association between HLA-G gene polymorphisms and SLE disease susceptibility. So far the study between HLA-G and SLE mainly focus on the Exon83’untranslated region(3’UTR), the association of HLA-G3’UTR with SLE evaluate mianly on the14-bp insertion/deletion (14-bpINS/DEL) and the+3142C/G polymorphisms. The other polymorphic sites have been studied only in Brazilian Populations, association studies of genetic polymorphisms in HLA-G3’UTR with SLE yet to be carried out in different populations. Human soluble HLA-G (sHLA-G) is an important molecule form in HLA-G gene expression which plays a role in immune systematic regulation. Previous researches have discovered that HLA-G3’UTR polymorphisms are associated with Human Soluble leucocyte antigen-G, its mechanism of action in SLE is worth further exploration.To assess the association between HLA-G3’UTR genetic polymorphisms with SLE and sHLA-G level in Yunnan, in this study a case-control study was carried out in349SLE patients and330healthy controls. Genotypes of8polymorphic sites(+296014-bpINS/DEL,+3003C/T,+3010C/G,+3027A/C,+3035C/T,+3142C/G,+3187A/G,+3196C/G) locus of3’UTR of the HLA-G gene were determined by PCR and DNA sequencing. Serum samples were collected from162SLE patients and sHLA-G levels were determined by enzyme-linked immunosorbent assay, to futher evaluate the association between HLA-G3’UTR polymorphisms with serum sHLA-G levels. Our results show that:(1)The allelic frequencies of+3027A/C,+3035C/T and+3196C/G have significant difference between patients and controls(P<0.05). Allelic and genotypic frequencies of14-bpINS/DEL,+3003C/T,+3010C/G,+3142C/G and+3187A/G in the3’UTR of the HLA-G gene have no significant difference between patients and controls(P>0.05). The frequencies of+3027A,+3035T and+3196C allele was higher in the SLE group compared with control group. In dominant inheritance model, the Odd Ratio of dominant genotype (AA+AC) and (CT+TT) are1.578(95%CI:1.153-2.160, P=0.004) and1.720(95%CI:1.260-2.348, P=0.0006) respectively in SLE. In recessive inheritance model, the Odd Ratio of dominant genotype CC is2.897(95%CI:1.229-6.830, P=0.015).(2)The frequencies of UTR-3(DTCCCGAC) have significant difference between patients and controls(P=0.003, OR=0.683,95%:0.530-0.881), The frequencies of UTR-7(ITCATGAC) have significant difference between patients and controls(P=0.005), the Odd Ratio is1.439(95%:1.115-1.857).(3) The difference of sHLA-G levels in different genotype of14-bpINS/DEL,+3003C/T,+3010C/G,+3027A/C,+3035C/T,+3142C/G,+3187A/G and+3196C/G polymorphisms have no significant (P>0.05).The analyses of3’UTR haplotypes showed that the difference of sHLA-G levels between UTR-1, UTR-3and UTR-7have no significant(P=0.369).Our results indicated that:(1)The genetic polymorphisms of the3’UTR of the HLA-G gene are associated with SLE susceptibility in people of Yunnan. The polymorphic sites+3027A/C,+3035C/T and+3196C/G are associated with SLE, the+3027A,+3035T and+3196C allele of the three polymorphic sites may be a risk factor for the incidence of SLE.(2)The analyses of3’UTR haplotypes showed that the haplotypes of the3’UTR of the HLA-G gene is associated with the development of SLE in people of Yunnan. UTR-3(DTCCCGAC) may was associated with protection against development of SLE. UTR-7(ITCATGAC) may was associated with SLE susceptibility in people of Yunnan.(3)We have not found significantly association between the genotypes and haplotypes of the3’UTR of the HLA-G gene with sHLA-G levels... |
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