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Association between susceptibility to rheumatoid arthritis and PADI4 polymorphisms: a meta-analysis

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Abstract

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, meta-analysis 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.

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Acknowledgments

The authors are grateful to Dr. G. Song for serving as a third reviewer. This study was supported in part by a grant of the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI13C2124).

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, 126-1, Anam-dong 5 ga, Seongbuk-gu, Seoul, 136-705, South Korea

    Young Ho Lee

  2. The Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul, South Korea

    Sang-Cheol Bae

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Lee, Y.H., Bae, SC. Association between susceptibility to rheumatoid arthritis and PADI4 polymorphisms: a meta-analysis. Clin Rheumatol 35, 961–971 (2016). https://doi.org/10.1007/s10067-015-3098-4

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