The Study On Association Of TLR4 Gene Polymorphisms With Systemic Lupus Erythematosus Of Han Population In Yunnan Province

Background and aims: Systemic lupus erythematosus (SLE) is an autoimmune disorder with the feature of autoantibodies production to a multitude of self-antigens. It can cause tissue and organs injury, and lead to many severe complicating diseases. Toll-like receptors 4(TLR4) plays a key role in innate immune and adaptive immune responses. It is predominantly activated by exogenous and endogenous ligands such as bacterial lipopolysaccharides (LPS), heat shock protein, fragment of hyaluronic acid. Activation of TLR4 can leads to activation of nuclear transcription factor such as NF-κB and expression of various inflammatory cytokines, which are important factors to both innate and adaptive immune. The aim of our study is to investigate the association between TLR4 single nucleotide polymorphisms and SLE in Yunnan Han Population.Methods: We recruited 553 SLE cases and 564 healthy controls from the Second Affiliated Hospital of Kunming Medical College. All samples are Han Population in Yunnan province and cases'diagnosis fulfilled the criteria of diagnostic guidelines draw up by America College of Rheumatology (ACR). We used polymerase chain reaction (PCR)-restriction fragment length polymerase (RFLP) and direct sequencing techniques to genotyping. The data is analysed by SPSS11.5, Arlequin 3.01, HaploView. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a logistic model.Results: 1)3 SNPs of TLR4 were all observed polymorphisms. 2)The single-locus analysis of rs11536889 showed it has no relationship with SLE. 3) GC heterozygote of rs41426344 and CT heterozygote, CC homozygote and C allele of rs10759932 may be the risk factors of SLE (adjusted P <0.05). 4) The frequencies of genotype and allele of rs41426344 are very close to the R24 group (6 Caucasian, 6 African American, 6 Asian, 6 Hispanic recruited from San Francisco Bay Area) in HapMap, indicated that might there is no distinct diversity among different population as to the SNP of this site. 5) The frequency of T alellel of rs10759932 in our control group is about 40% less than the CEU population. The G allele frequency of rs11536889 are as the same with Japanese population, while it is 11.05% lower than Caucansian polulation and 23.55% less than Yoruba population. These results showed in a certain extant that these two SNPs distribute variably in different ethnic groups and regions.Conclusion: This is the first time to analyse the relevance of TLR4 gene polymorphisms to SLE in Chinese Han Population in Yunnan Province. The present results show that TLR4 is a candidate gene related to SLE, and the TLR4 SNPs of rs41426344 and rs10759932 have been detected to be associated with SLE susceptibility. Moreover, the polymorphisms frequencies of TLR4 rs10759932 and rs11536889 are significant different among different ethnic groups.