Study On Relationship Between Polymorphism Site Of TLR5and9Genes And SLE Patients In Guangxi Zhuang And Han Population

Objective To investigate the correlation between single nucleotide polymorphism site of Toll-like Receptors5(TLR5)、TLR9and its transduction molecules in MyD88signaling pathway and the SLE patients of Guangxi Zhuang and Han population. And compare with their differences in role between the two nations.To clarify the role of each moleculars in the occurs and the development of SLE in Guangxi Zhuang and Han population in initially.Methods The single nucleotide polymorphism site of Toll-like Receptors5(TLR5)、TLR9and its transduction molecules in MYD88signaling pathway was detected by polymerase chain reaction-restriction fragment length polymorphism analysis technique(PCR-RFLP)、polymerase chain reaction-restriction enzyme digestion and direct sequencing of33cases of Zhuang population、44cases of Han population with SLE and72healthy control persons in Guangxi, analysising the correlation between the pathogenesis of SLE in Zhuang and Han population,and compare with the differences between the two groups in genotypes and allele frequencies.analysis in the two races,but also with SLE major clinical and laboratory parametera.Result1.The correlation of polymorphism of TLR5rs5744168and SLE patients in Guangxi Zhuang and Han population.(1) The TT genotype of TLR5rs5744168were missing in Guangxi Zhuang and Han populations of SLE and control groups;The CC genotype frequencies in each group were90.0%-100.0%.(2) The genotype frequencies of CC,CT and C、T allele frequencies in rs5744168site of TLR5were not statistically significant difference between from SLE of GuangXi Zhuang and Han Population and its control group,and the same in SLE of GuangXi Zhuang Population and its control、GuangXi Han Population and its control、SLE between the two nationals、controls between the two nationals (all P>0.05).(3) The polymorphism of rs5744168site of TLR5in patients whith SLE in Guangxi is not correlation whith ds-DNA-positive、ANA positive、kidney damage and other phenotype of clinical and laboratory test (all P>0.05).2. Comparativing and analysising the correlation of the gene polymorphism site of Toll-like Receptors9(TLR9)and its transduction molecules in MYD88signaling pathway and the SLE patients in Guangxi Zhuang and Han population.(1) The gene polymorphism site of TLR9and the SLE patients in Guangxi Zhuang and Han population.①The genotype frequencies and allele frequencies in rs352140site of TLR9were not statistically significant difference between from SLE of GuangXi Zhuang and Han Population and its control group,and the same in SLE of GuangXi Zhuang Population and its control、SLE between the two nationals、controls between the two nationals (all P>0.05). The genotype frequencies of TT in TLR9rs352140site is correlation with HanZu SLE,and it is significantly higher than the Han population in the control group (P=0.043);but it is not significant correlation between the Han population and its control group in C、T allele frequencies in rs352140site of TLR9(all P>0.05).②Analysising correlation between the genotype frequencies of TT and allele frequencies of T in rs352140site of TLR9and clinical and laboratory indicators in the case group of two nationalities:It is correlation with neuropsychiatric disease、ASO increased、ds-DNA-positive、ESR increased and the SLEDAI(all P<0.05);but it is not significantly correlation with facial rash、 light sensitivity、serositis、arthritis、Raynauds phenomenin、kidney damage and C3、C4、WBC thrombocytopenia、anti-cardiolipin antibodies、anti-SM antibodies、the ANA positive、the RF、CRP and other laboratory tests.(all P>0.05).(2) The gene polymorphism site of MyD88and the SLE patients in Guangxi Zhuang and Han population.①The genotype frequencies and allele frequencies in rs7744site of MyD88were not statistically significant difference between from SLE of GuangXi Zhuang Population and its control、GuangXi Han Population and its control、 SLE between the two nationals、controls between the two nationals (all P>0.05).②The allele frequencies of rs7744site of MyD88in SLE of GuangXi Zhuang and Han Population are different from the normal control group,and the difference is statistically significant(P=0.033). The genotype frequencies of and allele frequencies in rs7744site of MyD88are correlation with SLEDAI、ESR increased、arthritis、WBC thrombocytopenia(all P<0.05);but neuropsychiatric disease、ASO increased、ds-DNA-positive、ESR increased and the SLEDAI(all P<0.05);but are not significantly correlation with other observed clinical manifestations and laboratory parameters (all P>0.05).(3) The gene polymorphism site of TRAF6and the SLE patients in Guangxi Zhuang and Han population.①The genotype frequencies of GA+AA and the allele frequencies of A in rs5030472site of TRAF6were statistically significant difference between from SLE of GuangXi Zhuang Population and its control(P=0.006; P=0.004);And the same in SLE between the two nationals (P=0.024; P=0.014);But there are not statistically significant difference between from controls between the two nationals、SLE of GuangXi Zhuang and Han Population and its control group、 SLE of GuangXi Han Population and its control (all P>0.05).②In the case group of the two nationalities, the gene polymorphism site of TRAF6rs5030472is correlated with SLEDAI (P<0.05); The genotype frequencies is correlation with ASO increased (P=0.042);The allele frequencies of G/A is correlation with CRP(P=0.028);but the genotype frequencies and allele frequencies are not significantly correlation with other observed clinical manifestations and laboratory parameters (all P>0.05).(4) The gene polymorphism site of IRF5and the SLE patients in Guangxi Zhuang and Han population.①The genotype frequencies and the allele frequencies in rs2004640site of IRF5were statistically significant difference between from SLE of GuangXi Zhuang Population and its control (P=0.008; P=0.000);And the same in controls between the two nationals (P=0.031; P=0.002);But there are not statistically significant difference between from SLE between the two nationals、SLE of GuangXi Han Population and its control (all P>0.05).②The genotype frequencies and the allele frequencies in rs2004640site of IRF5were statistically significant difference between from SLE of GuangXi Zhuang and Han Population and its control (P=0.026; P=0.002);In the case group of the two nationalities, the genotype frequencies of GG/TT and allele frequencies of G/T of IRF5rs2004640is correlated with ds-DNA-positive and Raynauds phenomenin (all P<0.05); The allele frequencies of G/T is correlation with ASO increased、C3、C4、facial rash、light sensitivity and arthritis (all P<0.05). but the genotype frequencies and allele frequencies are not significantly correlation with other observed clinical manifestations and laboratory parameters (all P>0.05).Conclusion The data suggest that the TT genotype of TLR9rs352140might be susceptible gene for SLE in Han nationality in Guangxi,but the A allele genes of TRAF6rs5030472and the G allele genes of IRF5rs2004640might be susceptible allele gene for SLE in Zhuang nationality in Guangxi,so we speculate that the action of TLR9and its MYD88signaling pathway in the pathogenesis of SLE may be exist ethnic differences in Guangxi Zhuang and Han nationality; The gene polymorphism of TLR9and several transduction molecules in its MYD88signaling pathway may involve in the adjustment of SLE disease activity in varying degrees,suggesting that blocking the pathway at any level are likely to become a targets of active immunization.The gene polymorphism of rs5744168site of TLR5may be not significant related to susceptibility of SLE in GuangXi Zhuang and Han Population;...