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Peptidylarginine deiminase 4 -104C/T polymorphism and risk of rheumatoid arthritis: A pooled analysis based on different populations.

ABSTRACT: Many studies have analyzed the association between peptidylarginine deiminase 4 (PADI4) -104C/T polymorphism and rheumatoid arthritis (RA). However, the results are inconsistent. This meta-analysis, based on different populations, updated and reevaluated the possible associations between PADI4 -104C/T polymorphism and the susceptibility to RA.A literature search was performed on PubMed and related Chinese databases up to April 2017. The association between PADI4 -104C/T polymorphism and RA risk was evaluated by calculating pooled odds ratios (ORs) and 95% confidence intervals (CIs).A total of seventeen studies, including 5,756 RA cases and 4,987 controls, were screened out. In the overall population, PADI -104C/T polymorphism was significantly associated with an increased RA risk. In this meta-analysis stratified by ethnicity, a significant association between PADI -104C/T polymorphism and RA risk was established in China and Japan.Our study indicated a significantly increased association between PADI -104C/T polymorphism and RA in Chinese and Japanese populations. Because most included populations in this meta-analysis were Asian, further studies are needed to elucidate whether the PADI4 -104C/T gene confers RA in other ethnic groups.

SUBMITTER: Hua J

PROVIDER: S-EPMC5843217 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Peptidylarginine deiminase 4 -104C/T polymorphism and risk of rheumatoid arthritis: A pooled analysis based on different populations.

Hua Jiong J Huang Weijie W

PloS one 20180308 3

<h4>Background</h4>Many studies have analyzed the association between peptidylarginine deiminase 4 (PADI4) -104C/T polymorphism and rheumatoid arthritis (RA). However, the results are inconsistent. This meta-analysis, based on different populations, updated and reevaluated the possible associations between PADI4 -104C/T polymorphism and the susceptibility to RA.<h4>Methods</h4>A literature search was performed on PubMed and related Chinese databases up to April 2017. The association between PADI ...[more]

PMID: 29518108

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Project description:INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations. METHODS: A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations. RESULTS: The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)). CONCLUSION: Our study demonstrates an association between PADI4 and RA in the multiethnic population from South East Asia and suggests additional association with a PADI2 gene. The study thus provides further support for the notion that polymorphisms in genes for enzymes responsible for citrullination contribute to RA development in multiple populations of Asian descent.

Dataset Information

Peptidylarginine deiminase 4 -104C/T polymorphism and risk of rheumatoid arthritis: A pooled analysis based on different populations.

Publications

Peptidylarginine deiminase 4 -104C/T polymorphism and risk of rheumatoid arthritis: A pooled analysis based on different populations.

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