Panati Kalpana, Pal Sarvajeet, Rao K V, Reddy Vudem D
CPMB, Osmania University, Hyderabad 500 007, A. P., India.
Genes Genet Syst. 2012;87(3):191-6. doi: 10.1266/ggs.87.191.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting ~ 1% of the population worldwide. The genome wide association studies on RA patients revealed linkage with 1p36 locus containing peptidyl arginine deiminase 4 (PADI4) genes. Case-control association studies and mRNA stability assays reported the association of PADI4 gene with RA in Korean and Japanese populations. However, such association was not found in Spanish population. Differences in the association of PADI4 with RA in different populations prompted the present study in Indian population. Anti-CCP antibodies, RF antibody, disease activity scores at 28 joints (DAS28) and mutations in three exons of PADI4 were investigated in RA patients and control group. Among the patients anti-CCP antibody levels were found to be associated with high DAS28 values (r = 0.4526, P < 0.0001). Polymorphism in exon-4 (padi4_104, [rs1748033]) of PADI4 showed significant association of 'C' allele with RA in the study population (P = 0.0008). Polymorphism in exon-3 (padi4_92, [rs874881]) also exhibited moderate association with the disease (P = 0.075). However, no association of the disease was found with the SNPs padi4_89 [rs11203366] and padi4_90 [rs11203367] in exon-2 of PADI4.
类风湿性关节炎（RA）是一种慢性炎症性自身免疫性疾病，全球约1%的人口受其影响。对RA患者进行的全基因组关联研究显示，其与包含肽基精氨酸脱氨酶4（PADI4）基因的1p36位点存在连锁关系。病例对照关联研究和mRNA稳定性分析报告了PADI4基因与韩国和日本人群的RA有关联。然而，在西班牙人群中未发现这种关联。不同人群中PADI4与RA关联的差异促使了对印度人群的本研究。在RA患者和对照组中调查了抗环瓜氨酸肽（CCP）抗体、类风湿因子（RF）抗体、28个关节的疾病活动评分（DAS28）以及PADI4三个外显子中的突变情况。在患者中，发现抗CCP抗体水平与高DAS28值相关（r = 0.4526，P < 0.0001）。在研究人群中，PADI4外显子4（padi4_104，[rs1748033]）的多态性显示“C”等位基因与RA有显著关联（P = 0.0008）。外显子3（padi4_92，[rs874881]）的多态性也与该疾病呈现中度关联（P = 0.075）。然而，未发现该疾病与PADI4外显子2中的单核苷酸多态性padi4_89 [rs11203366]和padi4_90 [rs11203367]有关联。
