The objective of the study was to determine by meta-analysis whether polymorphisms of the gene encoding peptidylarginine deiminase 4 (PADI4) are associated with susceptibility to rheumatoid arthritis (RA). A literature review was conducted to identify data sets that described analyses of genetic association between PADI4 polymorphisms and RA. Data sets were collated and a meta-analysis was performed, with a specific focus on associations within Caucasian and Asian populations. A total of 15,947 RA cases and 22,696 controls that were taken from 28 studies in 24 papers were included in this study. Meta-analysis showed a significant association between allele 2 of the PADI4_94 polymorphism and RA in the overall population (odds ratio [OR]= 1.155, 95% confidence interval [CI]=1.069–1.249, p=2.7× 10−5). Stratification by ethnicity revealed an association between PADI4_94 allele 2 and RA in Asians (OR=1.273, 95% CI=1.193–1.359, p<1.0×10−9), but not in Caucasians (OR= 1.024, 95% CI=0.973–1.078, p=0.358). However, metaanalysis using homozygote contrast showed an association between PADI4_94 allele 2 and RA in both Asians (OR= 2.311, 95% CI= 1.1.858–2.875, p<1.0×10−9) and Caucasians (OR=1.523, 95% CI=1.157–2.004, p=0.008). Meta-analysis also revealed an association between allele 2 of the PADI4_104 polymorphism and RA in both Asians (OR=1.547, 95% CI=1.247–1.919, p=7.1×10−6) and Caucasians (OR=1.096, 95% CI=1.025–1.172, p=0.008). Finally, meta-analysis showed an association between allele 2 of the PADI4_92 polymorphism and RA in Asians (OR= 1.263, 95% CI=1.153–1.384, p=5.8×10−8), but not in Caucasians (OR=1.123, 95% CI=0.980–1.287, p=0.095). Meta-analysis indicated no association between allele 2 of either the PADI4_90 or PADI4_89 polymorphisms and RA in Asians. This meta-analysis revealed that the PADI4_94 and PADI_104 polymorphisms are associated with susceptibility to RA in Asians and Caucasians, and that the PADI4_92 polymorphism is associated with susceptibility to RA in Asians, but not in Caucasians.
- Rheumatoid arthritis
ASJC Scopus subject areas