ASSOCIATION BETWEEN SINGLE-NUCLEOTIDE POLYMORPHISMS IN TUMOR NECROSIS FACTOR-ALPHA GENE AND ANKYLOSING SPONDYLITIS IN CHINESE HAN POPULATION

Q. Cai, R. Chen , S. Duan , X. Han , B. Yang , L. He , S. Sun Rheumatology and Immunology, Changhai Hospital, Medical Genetics, The second Military medical university, Bio-X life science research center, Institute of Nutrition Science,chinese Academy of Sciences, Bio-X life science research center, Institute of Nutrition Science, Shanghai, ChinaObjectives: Objective. To examine single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha gene (TNFα) in Chinese Han population with ankylosing spondylitis (AS).Methods: Methods. An association analysis was performed in a case-control cohort of 107 AS cases and 116 controls. Seven SNPs located in the TNFαgene (T/C at position –1031 in promoter, C/A at position –863 in promoter, C/T at position –857 in promoter, G/A at position –308 in promoter, G/A at position –238 in promoter, C/T at position 488 in intron 1 and A/G at position 1303 in intron 3) were examined by direct sequencing and kinetic (real-time quantitative) PCR with allele-specific amplification. Haplotype inference software program was used to infer haplotype frequencies and the most likely haplotypes.Results: Results. The frequencies of allele T at position –857 and allele A at position –863 in the promoter of TNFαwere significantly increased in AS cases versus controls (P = 0.000003 and 0.0002, respectively), as were the genotype frequencie. No significant differences in genotype or allele frequencies at –308 and –238 loci were also noted. Highly significant differences in the overall distribution of haplotype frequencies based on 4 SNPs were evident between cases and controls, with the significant increases in the estimation of frequencies of the –1031T/-863C/-857T/-308G and –1031C/-863A/-857C/-308G haplotypes in the AS cases, but significant reduction in the frequencies of the –1031C/-863C/-857C/-308G and –1031T/-863C/-857C/-308G haplotypes in the AS cases compared with controls. Estimation of haplotype frequencies based on 3 and 2 SNPs indicated highly significant increases in the –1031T/-863C/-857T, –1031C/-863A/-857C, -863C/-857T and –863A/-857C haplotypes and significant decreases in the –1031T/-863C/-857C, –1031C/-863C/-857C and –863C/-857C haplotypes between AS cases and controls.Conclusion: Conclusion. Our data establish a highly significant disease association with –857 and –863 SNPs and the inferred haplotypes in the TNFαin AS of the Chinese Han population.Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 114Session: Genomics, genetics basis of disease and HLA/T cell recognition