Relationship Between The Polymorphism In The Third Intron Of Interferon-? Gene And Susceptibility To Neuromyelitis Optica

Neuromyelitis optica(NMO)is also called or Devic disease or De vic syndrome,due to it is first timed in 1894 by Devic.It is a kind of optic nerve involvement and spinal inflammatory demyelinating diseases,t he pathogenesis of which is not clear.NMO was once considered to be a subtype of MS,until the discovery of the specific antibody aquaporin4(AQP4)antibody,that is,NMO-IgG.In 2007,Wingerchuk proposed th econcept of neuromyelitis optica spectrum(NMOSD)and treated NMO-Ig G positive as one of the necessary conditions.With the development of t he understanding of NMOSD further study,the 2015 international NMO diagnostic group revised new diagnostic criteria,and NMO and NMOSD have been unified named NMOSD.Interferon gamma is produced by activated T cells and NK cells,also known as macrophage activating factor.It is the only member of ty pe II interferon,which has the characteristics of anti-virus,anti-tumor a nd immune regulation,and it can be involved in the inflammatory respo nse induced by the body's immune response.IFN-?gene is located on c hromosome 12 and comprised of four axons and three introns.In recent years,some studies have shown that IFN-may be involved in the patho genesis of NMOSD,and participate in the immune regulation of NMOS D patients.The results showed that the polymorphism of rs2430561 loc us was not associated with the onset of MS,and the polymorphism of rs2234685 locus was associated with the onset of MS.The role of gene polymorphism has not been studied in NMOSD.To explore the possible relationship between polymorphism in the first and third intron of IFN-?gene and the susceptibility of NMOSD,we detected rs2430561 and rs2234685 of IFN-? gene among normal and NMOSD groups.Objective:1To study the association between polymorphism in the first and th ird intron of IFN-? gene and the susceptibility to NMOSD,and reveal t he role of IFN-?in NMOSD.2 To investigate the changes of the serum levels of IFN-? in NMO SD,to define a possible pathogenic role of IFN-? during the progressio n of NMOSD.3 To investigate the associations between IFN-? gene polymorphism s and the serum levels of IFN-? in the acute-couse,EDSS scores,the dur ation of disease,and the number of relapses in NMOSD patient.4 To analyze the correlations of the serum levels of IFN-? to EDS S scores,the duration of disease,the number of relapses,and the age at onset.5 To analyze the correlations of EDSS scores to the serum levels of IFN-?,the duration of disease,the number of relapses,and the age at onset.6 To analyze the differences of the different subtypes about EDSS scores,the age at onset,the sex ratio,the duration of disease,and the number of relapses.Methods:1 A case-control research was performed on 50 NMOSD patients a nd 60 healthy individuals as control group.All subjects are Han nationa lity of northem China.All patients fulfilled the criteria of NMOSD prop osed by the 2015 international NMO diagnostic group.Sisty unrelated,he althy,randomly selected individuals from the same geographic area serve d as controls.None of the control subjects had a recorded personal or fa milial history of autoimmune disease.2 DNA was extracted from peripheral blood leukocytes by resin ty pe TM genomic DNA Extraction Kit.3 Rs2430561 and rs2234685 of IFN-gene in SNP were detected by gene sequencing.4 Serum samples were frozen in aliquots at-70? within 1h of col lection and repeated freezing and thawing of samples were avioded.Lev els of IFN-? in test and control subjects were determined by means of sandwich enzyme-linked immunosorbent assay(ELISA),using IFN-?immun oassay kits.5 The neurologic impairment status of patients was scored accordin g to the Expanded Disability Status Scale(EDSS),meanwhile collecting clinical data-the duration of disease,the age at onset,sex-ratio,and the nu mber of relapses.6 All statistical analyses were performed using SPSS 20.0 statistical analysis software.Genotype distribution underwent the Hardy-Weinberg(H W)equilibrium calculation,the two groups are presentative of the overall population.The ?2 test was used to compare genotype and allele freque ncies between the NMOSD and control population.Relmive risks(RRs)w ere calculated according to the methods of Woolf.The data of IFN-? le vels were expressed as Mean+S.Comparisons means in different groups were performed using Student t test or one—way ANOVA followed by Student-Newman—Keuls multiple range test.AP-value of less than 0.05 was considered statistically significant.Results:1The serum levels of IFN-? was found to be significantly increased in the acute-couse NMOSD group compared with the healthy control gr oup,(14.9892±5.1227)pg/ml VS(8.1623±7.8878)pg/ml,P<0.05,but n ot in the remitting-couse NMOSD group(P>0.05).While the serum level of IFN-? in the patients with acute-couse NMOSD were higher than in the patients with remitting-couse NMOSD(14.9892±5.1227)pg/ml VS(7.4697±5.6612)pg/ml,P<0.05.2 The detection of Hardy-Weinberg equilibrium(HWE):The genotype s of control were in Hardy-Weinberg equilibrium(HWE)(P>0.05).3 The mutation genotype was not detected in rs2234685,and 110 c ases were homozygous for AA.No significant difference of genotypes and site frequencies of IFN-? intron?(rs2430561)existed in NMOSD grou p compared with in the control group.(P>0.05).4 There was no significant difference in the serum levels of IFN-?in the acute-couse,EDSS scores,the age at onset,the duration of dis ease,the number of relapses and the BMI among NMOSD group with IFN-?(AA,AT,TT)respectively.5 In the NMOSD group,the EDSS score of acute-couse(4.24±2.32)and the remitting-couse(3.21±1.96)were significantly different(P <0.05).6 There was significant positive correlation in the EDSS scores to the duration of disease,the number of relapses,the age at onset and th e BMI(r=0.417,P=0.002,and r=0.257,P=0.000 and,r=0.565,P=0.000,and r=0.519,P=0.000,respectively).7 Viral infection and pregnancy may be the cause of NMOSD.Conclusions:1 50 cases of NMOSD patients with IFN-?intron rs2234685 locus were AA homozygous genotype.The IFN-? intron ?(rs2234685)gene po lymorphism might not be associated with NMOSD genetic susceptibility.2 The IFN-? intron ?(rs2430561)gene polymorphism might not be associated with NMOSD genetic susceptibility.3 The level of IFN-? in the patients with acute-couse NMOSD,but not in the patients with remitting-couse NMOSD.IFN-? might play an i mportant role in the development of NMOSD.4 There was no significant difference between the IFN-? polymorph ism and the serum levels of IFN-? in the acute-couse,the EDSS score,t he age of first onset,course of disease,number of onset and body mas s index.5 There was no significant difference between the serum levels of IFN-? in the acute-couse and the EDSS score,the age of first onset,co urse of disease,number of onset and body mass index.6 EDSS scores were positive correlation to the duration of disease,the number of relapses and the age at onset.7 Viral infection and pregnancy or abortion may be the cause of N MOSD.