Jinluo Cheng1, Hui Zhang, Chao Zhuang, Ruiping Liu. 1. Institute of Diabetes Research, Department of Orthopedics, and Central Laboratory, Affiliated Hospital of Nanjing Medical University, Changzhou Second People’s Hospital, Changzhou, China.
Abstract
OBJECTIVE: Peptidylarginine deiminase type 4 (PADI4) and methyl-CpG binding domain 4 (MBD4) are closely related with rheumatoid arthritis (RA). We hypothesized that PADI4 and MBD4 polymorphisms may contribute to RA susceptibility. METHODS: We studied PADI4 rs2240340 G/A, PADI4 rs874881 C/G, MBD4 rs140693 G/A, and MBD4 rs2005618 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: When the PADI4 rs2240340 GG homozygote genotype was used as the reference group, the AA genotype was associated with a significantly increased risk of RA. In the recessive model, when PADI4 rs2240340 GG/GA genotypes were used as the reference group, the AA homozygote genotype was associated with a significant increased susceptibility to RA. PADI4 rs874881 C/G was in complete linkage disequilibrium with PADI4 rs2240340 G/A. MBD4 rs140693 G/A and MBD4 rs2005618 T/C polymorphisms were not associated with the risk of RA. In stratification analyses, a significantly increased risk for RA associated with the PADI4 rs2240340 AA genotype was evident among older patients and patients who were anticitrullinated protein antibody (ACPA)-positive compared with the PADI4 rs2240340 GG/GA genotype. CONCLUSION: These findings suggest that the functional single-nucleotide polymorphism PADI4 rs2240340 G/A variant allele is associated with RA development, especially among older patients and ACPA-positive patients. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation by a larger study from a more diverse ethnic population is needed to confirm these findings.
OBJECTIVE:Peptidylarginine deiminase type 4 (PADI4) and methyl-CpG binding domain 4 (MBD4) are closely related with rheumatoid arthritis (RA). We hypothesized that PADI4 and MBD4 polymorphisms may contribute to RA susceptibility. METHODS: We studied PADI4rs2240340 G/A, PADI4rs874881 C/G, MBD4rs140693 G/A, and MBD4rs2005618 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: When the PADI4rs2240340 GG homozygote genotype was used as the reference group, the AA genotype was associated with a significantly increased risk of RA. In the recessive model, when PADI4rs2240340 GG/GA genotypes were used as the reference group, the AA homozygote genotype was associated with a significant increased susceptibility to RA. PADI4rs874881 C/G was in complete linkage disequilibrium with PADI4rs2240340 G/A. MBD4rs140693 G/A and MBD4rs2005618 T/C polymorphisms were not associated with the risk of RA. In stratification analyses, a significantly increased risk for RA associated with the PADI4rs2240340 AA genotype was evident among older patients and patients who were anticitrullinated protein antibody (ACPA)-positive compared with the PADI4rs2240340 GG/GA genotype. CONCLUSION: These findings suggest that the functional single-nucleotide polymorphism PADI4rs2240340 G/A variant allele is associated with RA development, especially among older patients and ACPA-positive patients. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation by a larger study from a more diverse ethnic population is needed to confirm these findings.