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Objective To systematically analyze and evaluate the association between the peptidylarginine deiminaseⅣ(PADI4) gene and rheumatoid arthritis (RA) based on the published data,and to provide evidence for the pathogenesis of RA.Methods By selecting five SNPs in PADI4 (rs11203366,rs11203367,rs874881,rs2240340,rs1748033) which had been extensively examined.Meta-analysis on each SNP was performed step by step according to Hugenet manual to investigate the association of the polymorphisms of the PADI4 gene with RA.Results This Meta-analysis enrolled 15 659 RA patients and 22 019 healthy controls from 21 studies worldwide.It demonstrated that rs11203366,rs11203367,rs2240340 and rs 1748033 confered susceptibility to RA in Asian ethnicity (P＜0.01,0.03,＜0.01,＜0.01),while rsl1203366,rsl1203367 and rs874881 confered susceptibility to RA in Caucasian of European ancestry (P=0.0002,0.004,0.03).It also shown that no significant association between rs874881 and RA in the Asian ethnicity populations (P=0.2),or rs2240340,rs1748033 and RA in Caucasian of European ancestry (P=0.18,0.1 ).A linkage disequilibrium study was also performed.The LD study showed that rs11203366,rs11203367,rs874881,rs2240340 and rs1748033 were in linkage disequilibrium both in the Asian ethnicity and Caucasian,which was basically inconsistent with the results of Meta-analysis.The conflicting results should be explained by many aspects such as bias in sample selection,genotyping,and the stratification.Conclusion The PADI4 genotype is partially associated with RA,and the underling mechanisms need further study.Haplotype based research and Metaanalysis would be valuable.
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Objective To investigate whether there is any consistent evidence of linkage across multiple studies,and to identify novel AS susceptibility loci by using GSMA method.Methods Genome-search Meta-analysis(GSMA)method was applied to genome scans of AS and spondyloarthropathy(SpA)to assess evidence for linkage across studies.Results Four AS genome scans including 479 families with 1151 affected individuals were used.Suggesting these BINS most likely contain AS-linked loci;BINS 6p22.3-p21.1,6pter-p22.3,17pter-p12,2p12-q22.1 and 5q34-qter.Four AS genome scans and one SpA scan including 544 families with 1,331 affected individuals were used.The GSMA produced genome-wide evidence for linkage on bin 6p22.3-p21 and 16q23.1-qter.Conclusion This GSMA added the evidence of the HLA loci as the greatest susceptibility factor to AS and shows evidences of chromosome 6,17p,2,5q and 16q as non-HLA susceptibility loci.