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Association of PD1.1 and PD1.6 polymorphisms with ankylosing spondylitis

Norberto Vibanco-Pérez1, Jorge Gutiérrez-Franco1, Ma De Jesús Duran-Avelar1, Juan Manuel Agraz-Cibrian1, Mariel Alejandra Jiménez-Alvarez1, Salvador Peña-Virgen2 and Jose Francisco Zambrano-Zaragoza1*
  • 1 Universidad Autónoma de Nayarit, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Mexico
  • 2 Instituto Mexicano del Seguro Social HGZ No. 1, Medicina Interna, Mexico

Ankylosing Spondylitis (AS) is the prototype of an interrelated group of rheumatic diseases now named spondyloarthritides (SpA), otherwise known as spondyloarthropathies. Clinical features of this disease include inflammatory back pain, asymmetrical peripheral oligoarthritis, enthesitis, and specific organ involvement, such as anterior uveitis, psoriasis and chronic inflammatory bowel disease [1].
AS is a chronic inflammatory disease primarily affecting the spine. Its major clinical features include sacroilitis, loss of spinal mobility and spinal inflammation. The chronic inflammation leads to fibrosis and ossification, where bridging spurs of bone known as syndesmophytes form, especially at the edges of the inter-vertebral discs, thus producing the ankylosing [2].
Although AS is of unknown aetiology, it is considered an autoimmune disease in which environmental and genetic factors are involved. [3]. It is known to be highly heritable, as >90% of the risk of developing the disease has been shown to be genetically determined [4]
The co-stimulatory pathways consisting of the PD-1 receptor and its ligands deliver inhibitory signals that regulate the balance among T cell activation, tolerance and immune-mediated tissue damage [5]. Various SNP in the PD1 gene have been identified, such as PD1.1 (rs36084323), PD1.3 (rs11568821), PD1.5 (rs2227981), and PD1.9 (rs2227982). Among these, PD1.3, PD1.5, and PD1.9 have been associated with autoimmune disorders in different ethnic groups [6]. In the case of AS, despite controversies among studies of the polymorphism associated with the disease, it appears that PD1.3, PD1.5 and PD1.9 are all candidates for association [7-11].
PD1 has been considered as a candidate because of their role in regulation for the immune homeostasis and in the maintenance of the peripheral tolerance through secondary co-stimulatory signaling in T cells. PD1.1 and PD1.6 are two single nucleotide polymorphisms, at -600 G/A (rs36084323), and +8669 G/A (rs10204225) respectively, that have been associated with others autoimmune diseases such as rheumatoid arthritis, type I diabetes mellitus, and systemic lupus erythematosus [12-14]. The aim of this work was to determine if the PD1.1 and PD1.6 polymorphisms are associated with AS in Mexican patients.
Thirty one patients with AS diagnosed at HGZ No. 1 from IMSS according to the current criteria [15], and 90 healthy subjects as a control group were included in the group. DNA was extracted from each subject and genotypification of PD1.1 and PD1.6 was carried out by using specific primers by bidirectional PCR amplification (Bi-PASA) of specific alleles by using previously reported primers [16]. Frequencies were determined, and odds ratio and CI95% were calculated. Our results showed no differences in the frequencies of neither PD1.1 (genotype AG or GG) nor PD1.6 between groups were found. However, the genotype PD1.1-AA showed statistically differences between groups (OR = 9.4286, 95%CI= 1.3648-65.1380), suggesting that it could be a risk factor, but it is necessary to increase the sample size in order to validate these association.

Acknowledgements

This work was supported in part by the Programa Integral de Fortalecimiento Institucional (PIFI) 2003-19-01 and 2010-18-MSU0019M-04

References

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Keywords: PD1 polymorphisms, PD1.6, PD1.1, ankylosing spondylitis, Association

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Immune-mediated disease pathogenesis

Citation: Vibanco-Pérez N, Gutiérrez-Franco J, Duran-Avelar M, Agraz-Cibrian J, Jiménez-Alvarez M, Peña-Virgen S and Zambrano-Zaragoza J (2013). Association of PD1.1 and PD1.6 polymorphisms with ankylosing spondylitis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00796

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Received: 17 Jun 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Jose Francisco Zambrano-Zaragoza, Universidad Autónoma de Nayarit, Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Tepic, Nayarit, Mexico, jzambran44@gmail.com