Correlativity Between STAT4Gene Polymorphisms And Primary Sjogren’s Syndrome (pSS)

Objective: Primary Sjorgen’s syndrome (pSS) is a kind of chronicautoimmune disease with the characteristics of lymphocyte infiltrating in theexocrine glands, occurrence of varieties of antoantibodies and multisystemimpairment. The incidence of pSS is about0.3%-0.7%in China. It is afrequently encountered and common disease which severely harms to humanhealth. The pathogenesis of pSS has not been very clear yet. This study testedthe STAT4gene polymorphisms in patients with primary Sjogren’s syndrome,analysed the correlation of this gene polymorphism with autoantibodyexpression, the pathological grades of labial salivary glands and diseaseactivity in order to explore the role of this gene polymorphism in thepathogenesis of pSS.Methods:1.The89patients were selected at Department ofRheumatology and Clinical Immunology in Hebei Provincal People’s Hospitalfrom May2011to November2011. All patients fitted to the criteria of2002SS international classification.109cases of healthy individuals were taken ascontrols from the centor of health examination in Hebei Provincal People’sHospital at same periods.2.Testing the STAT4gene rs7574865polymorphiclocus genotypes By PCR-RFLP testing technology.3. Detecting the anti-SSAantibody and anti-SSB antibody by Western blot, the rheumatoid factors(RF) by rate nephelometry and the Anti-nuclear antibody（ANA） byIndirect Immunofluorescence(IIF).4.The assessment of the disease activity ofpSS patients by means of the2009European League Against Rheumatism(EULAR) SS disease assessment index (ESSDAI).5. The pathologicalgrades of labial salivary glands: firstly taking out the labial salivary glands,and then fixing it with formalin, embedded in paraffin wax, sectioned theglands, staining by HE and finally proceeding the grades of lymphocyte infiltration according to the Chisholm criteria.6. Using SPSS13.0software forStatistical analysis.Results：1The distribution of genotype and allele of the STAT4rs7574865polymorphism sites in pSS patients and normal individuals: In the pSS group,the genotype frequencies of STAT4rs7574865GG, GT, TT were32.6%,55.0%,12.4%respectively, the allele frequencies of T, G were39.9%,60.1%.In the control group, the genotype frequencies of STAT4rs7574865GG, GT,TT were54.1%,40.4%,5.5%respectively, the allele frequencies of T, G were25.7%,74.3%. Between the pSS group and control group, the difference of thedistribution of the GG, GT, TT genotypes frequencies and the difference ofthe distribution of the T allele frequencies both had statistical significance (P<0.05and P<0.01respectively).2The distribution of T, G allele of the STAT4rs7574865polymorphismsites in anti-SSA antibody-positive and-negative pSS patients: There were38cases with anti-SSA antibody-positive, whose allele frequencies of T, Gwere50.0%,50.0%, and there were51cases with anti-SSA antibody-negative,whose allele frequencies of T, G were32.4%,67.6%. Between the anti-SSAantibody-positive and anti-SSA antibody-negative pSS groups, the differenceof the T allele frequencies had statistical significance（P<0.05）.3The distribution of T, G allele of the STAT4rs7574865polymorphismsites in anti-SSB antibody-positive and-negative pSS patients: There were34cases with anti-SSB antibody-positive, whose allele frequencies of T, G were51.5%,48.5%, and there were55cases with anti-SSB antibody-negative,whose allele frequencies of T, G were32.7%,67.3%. Between the anti-SSBantibody-positive and anti-SSB antibody-negative pSS groups, the differenceof the T allele frequencies had statistical significance（P<0.05）.4The distribution of T, G allele of the STAT4rs7574865polymorphismsites in RF-positive and-negative pSS patients: There were40cases withRF-positive, whose allele frequencies of T, G were41.3%,58.7%, and therewere49cases with RF-negative, whose allele frequencies of T, G were 38.8%,61.2%. Between the RF-positive and RF-negative pSS groups, thedifference of the T allele frequencies had no statistical significance（P＞0.05）.5The distribution of T, G allele of the STAT4rs7574865polymorphismpoints in ANA-positive and-negative pSS patients: There were61cases withANA-positive, whose allele frequencies of T, G were41.8%,58.2%, andthere were28cases with ANA-negative, whose allele frequencies of T, Gwere35.7%,64.3%. Between the ANA-positive and ANA-negative pSSgroups, the difference of the T allele frequencies had no statisticalsignificance（P＞0.05）.6The relationship of T, G allele frequencies of the STAT4rs7574865polymorphism sites with the disease activity index in pSS patients: Thedisease activity index of pSS patients were divided into four grades: score0-2for level1, score3-5for level2, score6-8for level3, score9or more for level4. The numbers of pSS patients in level1, level2, level3and level4were21,33,24and11respectively. The allele frequencies of T, G in level1, level2,level3and level4were38.1%,61.9%, and47.0%,53.0%, and31.3%,68.7%,and41.0%,59.0%respectively. Among the pSS patients wtih different diseaseactivity index levels, the difference of the T allele frequencies had nostatistical significance（P＞0.05）.7The relationship of T, G allele frequencies of the STAT4rs7574865polymorphism sites with the pathological grades of labial salivary glands inpSS patients: There were57cases with the grade4, whose allele frequenciesof T, G were43.0%,57.0%and there were23cases with the grade3, whoseallele frequencies of T, G were41.3%,58.7%. Btween the pSS patients withthe grade4and the grade3, the difference of the T allele frequencies had nostatistical significance（P＞0.05）.Conclusion:1In the pSS group, the T allele frequency of STAT4rs7574865wassignificantly higher than that in the control group. Btween the two groups, thedifference of the T allele frequencies had statistical significance, suggestingthat the T allele of STAT4rs7574865is a risk of pSS disease. 2The T allele frequencies of pSS patients with anti-SSAantibody-positive and anti-SSB antibody-positive were significantly higherthan those in the pSS patients with anti-SSA antibody-negative and anti-SSBantibody-negative. Btween the corresponding two groups, difference of theT allele frequencies had statistical significance, suggesting that the T allelecarried by pSS patients was associated with the expression of anti-SSA andanti-SSB antibodies.3The T allele frequencies of pSS patients with RF-positive and ANAantibody-positive were slightly higher than that in the pSS patients withRF-negative and ANA antibody-negative. But between the corresponding twogroups, difference of the T allele frequencies had no statistical significance,suggesting that the T allele carried by pSS patients was not associated with theexpression of RF and ANA.4Among the pSS patients with different levels of disease activity indexand btween pathological grade4and3of labial salivary glands, bothdifferences of the T allele frequencies had no statistical significance,suggesting that the T allele carried by pSS patients was not associated with thedisease activity and the pathological grades of labial salivary glands of pSS.