Zavala-Cerna Maria Guadalupe, Gonzalez-Montoya Norma Guadalupe, Nava Arnulfo, Gamez-Nava Jorge I, Moran-Moguel Maria Cristina, Rosales-Gomez Roberto Carlos, Gutierrez-Rubio Susan Andrea, Sanchez-Corona Jose, Gonzalez-Lopez Laura, Davalos-Rodriguez Ingrid Patricia, Salazar-Paramo Mario
Programa Internacional del ICB, Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, JAL, Mexico.
Unidad de Investigación en Epidemiología Clínica, Hospital de Especialidades, Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Clin Dev Immunol. 2013;2013:383681. doi: 10.1155/2013/383681. Epub 2013 Dec 22.
Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.
肽基精氨酸脱亚氨酶IV（PAD 4）是一种负责称为瓜氨酸化的翻译后修饰的酶，它产生了抗环瓜氨酸化肽抗体（ACPA）所识别的抗原决定簇。在PADI4基因中已描述了四个单核苷酸多态性（SNP），形成类风湿性关节炎（RA）的易感性单倍型；然而，不同人群的关联研究结果似乎相互矛盾。本研究的目的是分析PADI4基因易感性单倍型（GTG）中三个SNP的存在是否与RA患者的ACPA阳性相关。这是一项横断面研究，纳入了86例RA患者和98例健康对照。对PADI4基因中的PADI4_89、PADI4_90和PADI4_92多态性进行基因分型。易感性单倍型（GTG）在RA患者中更为常见；有趣的是，我们发现了一种与RA相关的新单倍型，其频率更高（GTC）。多态性与西班牙HAQ-DI和DAS-28的高分之间没有关联，但我们确实发现RARBIS指数与PADI4_89、PADI4_90多态性之间存在关联。我们无法证实易感性单倍型的存在与ACPA阳性之间存在关联。关于该基因蛋白质组表达的进一步证据将确定其在抗原产生和自身免疫中的作用。
