| The study of TNF-a single nucleotide polymorphism in DM patientsObjective:To investigate the tumor necrosis factor alpha gene single nucleotide polymorphism (SNP) in dermatomyositis (DM) patients.Contents and Methods:The first part: To study the association of TNF-αpromoter -308A/G polymorphism and DM-A Meta analysis. Methods:We searched all the publications about the association between TNF-αpromoter -308A/G polymorphism and DM from PubMed, EBSCO, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese). Meta-analysis was performed for genotypes AA versus GG, GA versus GG, AA versus GG+GA, GA+AA versus GG, and A allele versus G allele in a fixed/random effect model.The second part:To study the association of TNF-a gene polymorphism and DM in a Chinese Han population. Methods:A case-control study of three TNF-αSNPs were undertaken, comparing cases of DM(n=82) patients with normal subjects(n=113).To determine the genotype of every subject, the technique of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP) was used.The third part: To study the association of serum TNF-αlevel and TNF-αgene polymorphism in different groups (cases and controls). Methods: Using Elisa method to detect serum TNF-αlevel in both DM and healthy control subjects, and calculate the association of genotypes or haplotypes with serum TNF-αlevel.Results:The first part: A total of 5 studies (279 cases and 213 controls) were included in the current Meta-analysis. When all groups were pooled, significant association of A allele and increased DM risk was found (OR=2.48,95%CI=2.00-3.07,P<0.001). When analyses were restricted to more race homogeneous populations, significant association of A allele and increased DM risk was found in Caucasian population (OR=2.50,95%CI=1.99-3.14, P<0.001). Significant association between TNF-αpromoter-308 polymorphism and DM was observed when examining the contrast of AA+GA versus GG, AA versus GA+GG, AA versus GG, and GA versus GG.The second part:The genotypes and alleles frenquencies in the three TNF-αSNPs(-238,-308,and-1031) had no significant differences between DM and normal subjects. The haplotype AGT (-238,-308,-1031) frequency was zero in DM patients, which was significantly increased in controls(4.76%) vs DM subjects(P=0.01).The third part:Serum TNF-αlevel was significantly increased in DM patients compared with healthy controls(P=0.0006). The serum TNF-αlevel had no significant differences in different genotypes or haplotypes.Conclusion:This Meta-analysis demonstrated significant association between TNF-αpromoter -308A/G polymorphism and DM in Caucasian populations, implying that TNF-α-308A allele was a risk factor in Caucasian DM patients. No association was detected between TNF-α-308/-238/-1031 polymorphism and DM in a Chinese Han population. The TNF-αgene (-238,-308,-1031) haplotype AGT was a protective factor in Chinese DM patients. Serum TNF-αlevel was significantly increased in DM patients compared with healthy control subjects. No association was detected between TNF-α-308/-238/-1031 polymorphism and serum TNF-αlevel in different groups. |
