Publications (12)14.26 Total impact
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Article: The -319C/+49G/CT60G Haplotype of CTLA-4 Gene Confers Susceptibility to Rheumatoid Arthritis in Mexican Population.
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ABSTRACT: Several single nucleotide polymorphisms (SNPs) within the CTLA-4 gene and elevated serum levels of soluble CTLA-4 (sCTLA-4) have been associated with autoimmunity including rheumatoid arthritis (RA). In this case-control study, we evaluated the relationship between the -319C/T (rs5742909) and CT60 G/A (rs3087243) SNPs and sCTLA-4 levels in 200 RA patients and 200 control subjects (CS) from Western Mexico. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique and the sCTLA-4 levels were quantified using an enzyme-linked immunosorbent assay kit. In addition, we performed a haplotype analysis, including our previous data of the +49A/G (rs231775) SNP. The G/A genotype of the rs3087243 SNP was associated with a decreased risk of RA [odd ratio (OR) 0.61, 95 % confidence interval (CI) 0.38-0.96, p = 0.024]. This protection was also observed in the negative anti-cyclic citrullinated peptide group of RA carriers of the A allele (OR 0.48, 95 % CI 0.22-1.05, p = 0.042). On the contrary, we identified the -319C/+49G/CT60G haplotype of CTLA-4 gene as a risk factor for RA (OR 1.69, 95 % CI 1.13-2.52, p = 0.01). The sCTLA-4 levels were not associated with RA (p = 0.377), but were correlated with the functional disability of these patients (r = 0.282, p = 0.012). However, in CS the C/T genotype of the rs5742909 SNP, as well as the G/G and G/A genotypes of the rs3087243 SNP were associated with higher sCTLA-4 levels (p < 0.001). In conclusion, our results suggest that the -319C/+49G/CT60G haplotype of CTLA-4 gene is a genetic marker of susceptibility to RA in Western Mexico, whereas the rs3087243 SNP confers protection against this disease. Moreover, both SNPs showed an effect on the sCTLA-4 production in our control population. However, further studies are required to evaluate the role of sCTLA-4 in RA, as well as the molecular and functional basis of the association between both CTLA-4 gene SNPs and soluble levels of CTLA-4 in CS.Cell biochemistry and biophysics 05/2013; · 3.34 Impact Factor -
Article: The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico.
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ABSTRACT: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The PTPN22 gene encodes lymphoid tyrosine phosphatase LYP, a potent negative regulator of T cell activation. Polymorphic variants of this gene have previously been associated with various autoimmune disorders. The +1858C/T single-nucleotide polymorphism (SNP) (rs2476601), in the exon 14 of the PTPN22 gene has been associated with susceptibility to RA in several population. The aim of this work was to investigate whether the +1858C/T of the PTPN22 gene is associated with susceptibility to RA in Western Mexico population. A total of 309 unrelated RA patients, classified according to American College of Rheumatology (ACR) 1987 criteria, as well as 347 controls residents from Western Mexico were recruited for this study. The DNA samples were genotyped for +1858C/T PTPN22 gene SNP using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). The frequency of +1858T risk allele was significantly increased in patients with RA compared with controls (p=0.001, OR=2.83, 95%CI=1.50-5.32). To confirm this results we established a comparison between subjects carrying of CT+TT genotypes versus those carrying CC genotype, between both groups (p=0.004, OR=2.65, 95%CI=1.33-5.36). Nevertheless, we not observed association of the +1858C/T PTPN22 gene SNP with clinical activity and functional disability in RA patients. Likewise, the +1858T variant in RA patients seropositive for anti-CCP antibodies, increased the risk for RA (p=0.008, OR=2.5, 95%CI=1.3-5.0) when we compared with controls; however, in the group of seronegative patients, no was found significant difference (p=0.1, OR=2.5, 95%CI=0.9-7.2). Our results support the association of the +1858T risk allele of the +1858C/T PTPN22 polymorphism with susceptibility to RA and confirm that, in combination with anti-CCP antibodies, this SNP influence the autoimmune processes towards a development of RA in Mexican population.Immunology letters 06/2012; 147(1-2):41-6. · 2.91 Impact Factor -
Article: Plasminogen activator inhibitor-1 C/G polymorphism in relation to plasma levels in rheumatoid arthritis
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ABSTRACT: Plasminogen activator inhibitor type 1 (PAI-1) is an inhibitor of plasmin production. Plasmin can directly or indirectly to degrade cartilage and bone matrix. The PAI-1 HindIII polymorphism has been associated with high PAI-1 plasma levels in myocardial infarction patients and control populations. Furthermore, it has been associated with the angiographic extent of coronary artery disease, but their involvement in other diseases is still uncertain. Here, we assessed the relationship between PAI-1 HindIII polymorphism and PAI-1 plasma levels in rheumatoid arthritis (RA). One hundred and twenty-five RA patients and 132 control subjects (CS) were included. Genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism technique and PAI-1 plasma levels were quantified using an ELISA kit. Not significant differences in genotype and allele frequencies between both studied groups were observed (P>0.05). RA patients showed lower PAI-1 plasma levels (18.92±12.94ng/ml) than CS (23.68±23.38ng/ml), without significant difference (P=0.299). However, in RA patients the C/G genotype carriers showed higher PAI-1 plasma levels (23.00±13.81ng/ml) with respect to C/C (16.77±11.97ng/ml) and G/G (10.47±7.07ng/ml) genotype carriers (P=0.036). The PAI-1 HindIII polymorphism was not associated with RA susceptibility. However, the C/G genotype is associated with high PAI-1 plasma levels in RA patients.Clinical and Experimental Medicine 04/2012; 9(3):223-228. · 1.58 Impact Factor -
Article: The functional class evaluated in rheumatoid arthritis is associated with soluble TGF-β1 serum levels but not with G915C (Arg25Pro) TGF-β1 polymorphism.
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ABSTRACT: The influence of genetic factors in rheumatoid arthritis (RA) has been described, including several cytokine genes such as transforming growth factor β (TGF-β) with regulatory effects on lymphocytes, dendritic cells, macrophages, chondrocytes, and osteoblasts, which are important in the RA pathogenesis. The G915C TGF-β1 polymorphism has been associated with soluble TGF-β1 (sTGF-β) serum levels. Thus, we studied the association of G915C (Arg25Pro) TGF-β1 polymorphism with sTGF-β1 serum levels in RA. We enrolled 120 RA patients and 120 control subjects (CS). The G915C TGF-β1 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and sTGF-β1 serum levels were quantified using an ELISA kit. The genotype frequency of G915C TGF-β1 polymorphism in RA and CS was G/G (91.7%), G/C (8.3%), C/C (0%) and G/G (85.8%), G/C (14.2%), C/C (0%), respectively, without significant differences. Moreover, the G/G TGF-β1 genotype carriers presented the highest disability index evaluated for the Spanish HAQ-DI score (P < 0.001). In addition, the sTGF-β1 serum levels were higher in RA (182.2 ng/mL) than CS (160.2 ng/mL), there was not significant difference. However, we found a positive correlation between the sTGF-β1 serum levels and the functional class (r = 0.472, P = 0.023). In conclusion, the G915C (Arg25Pro) TGF-β1 polymorphism is not associated with RA, but the sTGF-β1 serum levels are related with the functional class in RA.Rheumatology International 11/2010; 32(2):367-72. · 1.88 Impact Factor -
Article: A functional Ser(413)/Ser(413) PAI-2 polymorphism is associated with susceptibility and damage index score in systemic lupus erythematosus.
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ABSTRACT: Systemic lupus erythematosus in some cases is characterized for development of thrombotic events with a significantly increased risk of mortality. The frequencies and clinical associations of Ser(413)/Cys(413) PAI-2 polymorphism in 40 systemic lupus erythematosus, 50 rheumatoid arthritis patients, and 100 healthy subjects were investigated. The Ser(413)/Ser(413) genotype frequency was 53% (lupus), 36% (rheumatoid arthritis), and 35% (healthy subjects). The Ser(413) allele was associated with systemic lupus erythematosus (P = .04, odds ratio = 1.76, 95% confidence interval = 1.01-3.06). In all, 4 patient carriers of Ser(413)/Ser(413) genotype, developed thrombotic events. The lupus patients identified with Ser( 413)/Ser(413) genotype showed an increased damage (57%), compared with Ser(413)/Cys(413) and Cys(413)/Cys(413) genotypes, with significant difference (P = .03). These findings suggest an association of Ser( 413) /Ser( 413) genotype with greater damage index score and Ser( 413) allele with systemic lupus erythematosus. Besides, PAI-2 polymorphism could be related with thrombotic phenomena in systemic lupus erythematosus.Clinical and Applied Thrombosis/Hemostasis 10/2008; 15(2):233-8. · 1.33 Impact Factor -
Article: Distribution of --844 G/A and Hind III C/G PAI-1 polymorphisms and plasma PAI-1 levels in Mexican subjects: comparison of frequencies between populations.
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ABSTRACT: Several polymorphisms have been described in the PAI-1 gene including the -844 G/A and Hind III C/G polymorphisms. These polymorphisms have been associated with different diseases such as preeclampsia and cardiovascular diseases. The allele and genotype frequencies of both PAI-1 polymorphism where investigated in Mexican subjects and compared with other healthy worldwide populations. The hematological and biochemical parameters where classified according each genotype in our studied group. One hundred Mexican subjects were recruited. Demographic data and hematological and biochemical parameters were collected, and genomic DNA isolation was performed in all the participants. Screening of both polymorphisms studied was made by polymerase chain reaction and restriction analysis. Levels of plasminogen activator inhibitor-1 in plasma were measured by ELIS-ARA plasminogen activator inhibitor antigen kit. The -844 and Hind III genotypes frequencies were as follows: 49% (G/G), 40% (G/A), 11% (A/A) and 50% (C/C), 44% (C/G), 6% (G/G), respectively. The wild-type genotypes (G/G and C/C) were significantly higher with respect to the compared populations. In addition, a significant increase of apolipoprotein A1 in the carriers of G/A -844 and C/G Hind III genotypes was observed. However, when the plasma plasminogen activator inhibitor levels were analyzed with respect to each genotype and haplotype, no significant differences were found.Clinical and Applied Thrombosis/Hemostasis 05/2008; 14(2):220-6. · 1.33 Impact Factor -
Article: The -844 G/A PAI-1 polymorphism is associated with mRNA expression in rheumatoid arthritis.
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ABSTRACT: We assessed whether the -844 G/A polymorphism and mRNA expression of plasminogen activator inhibitor 1 (PAI-1) gene are associated with rheumatoid arthritis (RA). Demographic data, hematological, biochemical parameters, disease activity-disability indexes, -844 G/A genotypes and mRNA expression levels of the PAI-1 gene were determined in 50 RA patients and 50 healthy subjects (HS). Non-significant differences in genotype and allele frequencies related to -844 G/A polymorphism in RA versus HS, were found. High mRNA expression of the PAI-1 gene, was demonstrated in RA versus HS (P < 0.05). In addition, A/A genotype carriers showed increase of PAI-1 mRNA expression (3.1-fold) respect to G/G and G/A genotypes in RA patients (P < 0.05). Our finding suggest an association of A/A -844 PAI-1 genotype with high PAI-1 mRNA expression in RA patients.Rheumatology International 03/2008; 28(4):355-60. · 1.88 Impact Factor -
Article: Identificación del polimorfismo G915C en el gen del factor de crecimiento transformante-b1 (TGF-b1) en pacientes con osteoartritis de rodilla
Bioquimia. 01/2007; -
Article: Impacto del polimorfismo -844 g/a del gen PAI-1 sobre la expresión del mrna en artritis reumatoide
Bioquimia. 01/2007; -
Article: Distribución del polimorfismo G915C (ARG25PRO) en el gen del TGF-b1 en pacientes con artritis reumatoide del occidente de México
Bioquimia. 01/2007; -
Article: Polimorfismo Hind III del gen PAI-1 y niveles de expresión de la proteína PAI-1 en pacientes con artritis reumatoide
Bioquimia. 01/2007; -
Article: Distribución del polimorfismo A561→C del gen de e-selectina en pacientes Mestizos mexicanos con osteoartritis y artritis reumatoide
Bioquimia. 01/2006;
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Institutions
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2012
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Universidad de Guadalajara
- Departamento de Biología Molecular y Genómica
Guadalajara, Jalisco, Mexico -
Centro Universitario de Ciencias de la Salud
Guadalajara, Jalisco, Mexico
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