Norma Torres-Carrillo

The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico.

INTRODUCTION 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. OBJECTIVE 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. METHODS 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). RESULTS 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). CONCLUSIONS 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.

A Functional Ser413/Ser413 PAI-2 Polymorphism Is Associated With Susceptibility and Damage Index Score in Systemic Lupus Erythematosus

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 Ser413/Cys413 PAI-2 polymorphism in 40 systemic lupus erythematosus, 50 rheumatoid arthritis patients, and 100 healthy subjects were investigated. The Ser413/Ser413 genotype frequency was 53% (lupus), 36% (rheumatoid arthritis), and 35% (healthy subjects). The Ser413 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 Ser413/Ser413 genotype, developed thrombotic events. The lupus patients identified with Ser 413/Ser413 genotype showed an increased damage (57%), compared with Ser413/Cys413 and Cys413/Cys413 genotypes, with significant difference (P = .03). These findings suggest an association of Ser413/Ser413 genotype with greater damage index score and Ser413 allele with systemic lupus erythematosus. Besides, PAI-2 polymorphism could be related with thrombotic phenomena in systemic lupus erythematosus

Genotype Ser413/Ser of PAI-2 polymorphism Ser413/Cys is associated with anti-phospholipid syndrome and systemic lupus erythematosus in a familial case: comparison with healthy controls.

Background: We describe a family with a 7‐year‐old proband case diagnosed with systemic lupus erythematosus (SLE) plus secondary anti‐phospholipid syndrome (APS) as well as two affected paternal aunts. We compared the frequency of these polymorphisms with healthy controls. Objectives: To evaluate the mode of inheritance in this familial case of APS and SLE and the possible association of plasminogen activator inhibitor‐1 (PAI‐1) −675 4G/5G and PAI‐2 Ser413/Cys polymorphisms. To compare the genotype frequency of these polymorphisms with the results found in a Mexican Mestizo population. Methods:PAI‐1 −675 4G/5G and PAI‐2 Ser413/Cys were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) technique using Bsl I and Mwo I on four generations of the family studied. PAI‐2 Ser413/Cys polymorphism was also determined in 50 healthy individuals of Mexican Mestizo origin. Results: The family pedigree demonstrated that this family did not follow a Mendelian inheritance pattern. When the PAI‐2 Ser413/Cys polymorphism was examined, we found that 60% (3/5) of the relatives homozygous to Ser413/Ser were affected with SLE and/or APS (p = 0.027). The proband case was 4G/5G genotype for the PAI‐1 −675 4G/5G polymorphism. No differences between healthy controls of the Mexican Mestizo population and the family studied for the PAI‐2 Ser413/Cys polymorphism or PAI‐1 −675 4G/5G polymorphisms were found. Conclusions: Our data indicate that this family did not follow the Mendelian inheritance pattern. The Ser413/Ser genotype demonstrated in 60% of the affected members (3/5) of this family might increase the risk for autoimmune syndromes such as APS or SLE.

Circulating TNFRI and TNFRII levels correlated with the disease activity score (DAS28) in rheumatoid arthritis

Objective: To measure levels of soluble tumour necrosis factor alpha (TNFα) receptor type I (sTNFRI) and type II (sTNFRII) in order to correlate them with C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and disease activity score (DAS28) in RA patients. Methods: We recruited 41 RA patients classified according to American College of Rheumatology (ACR) criteria and 38 healthy subjects (HS). sTNFRI and sTNFRII were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Clinical activity in RA patients was evaluated using the Disease Activity Score using 28 joint counts (DAS28). The statistical analysis was realized using SPSS version 10.0. Results: Soluble TNFRI and TNFRII levels were higher in RA patients (p = 0.04 and 0.001, respectively) than HS. Serum levels of sTNFRI correlated with sTNFRII (r = 0.699, p < 0.0001). sTNFRII correlated with DAS28 (r = 0.375, p = 0.017), RF (r = 0.505, p = 0.004), and ESR (r = 0.323, p = 0.042). Conclusion: The increased levels of both sTNFRI and sTNFRII suggest a secondary event related to the inflammatory state observed in RA, whereas the correlation of sTNFRII with RF, ESR, and DAS28 reflects the preferential TNFRII shedding induced by TNFα. sTNFRII may be useful as an additional inflammatory marker in RA.

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

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.

Association of low serum 25-hydroxyvitamin D levels with the frailty syndrome in Mexican community-dwelling elderly

Abstract Objective: Since vitamin D is an important regulator of muscle function, the effect of vitamin D deficiency on frailty syndrome has been recently studied. This cross-sectional study aimed to determine the association between 25(OH)-vitamin D levels and frailty status in Mexican community-dwelling elderly. Methods: Sample of 331 community-dwelling elderly aged 70 or older, a subset of those included in the “Coyoacán cohort” were included. 25(OH)-vitamin D assay and frailty status were measured. Results: Mean age was 79.3 years and 54.1% were women. Those classified as frail were more likely to have lower Mini-Mental State Examination score (p = 0.015), more disability for instrumental activities of daily living (p < 0.001) and for activities of daily living (p < 0.001). Serum 25(OH)-vitamin D levels were lower in the frail subgroup when compared with the non-frail one (p < 0.001). Multivariate logistic regression analyses showed a significant association between intermediate tertile [odds ratios (OR) = 4.13; 95% confidence intervals (CI) 2.00–8.56] or insufficient tertile (OR = 8.95; 95% CI 2.41–33.30) of vitamin D levels and frailty even after adjusting for potential confounders. Conclusion: These results suggest that older adults with low 25(OH)-vitamin D levels are associated with the probability to being frail compared with those with sufficient vitamin D levels.

Interleukin-17A Levels Vary in Relapsing-Remitting Multiple Sclerosis Patients in Association with Their Age, Treatment and the Time of Evolution of the Disease

Objective: The present study was specifically designed to discern the possible existence of subgroups of patients with the relapsing-remitting form of multiple sclerosis (RRMS) depending on their gender, age, disease stage (relapsing or remitting), time of disease evolution and response to different treatments. Methods: We analyzed samples from patients with RRMS (50 females and 32 males) and healthy individuals (25 matched for age and gender) and determined serum concentrations of IFN-γ, IL-10 and IL-17A. We stratified patients by gender, age, treatment and disease evolution time, and subsequently correlated these independent variables with the concentrations of the previously mentioned cytokines. Results: We provided initial evidence that treatment exerted possible differential effects depending on the time of disease duration. Results evidence the existence of different subgroups of patients with MS, who can be classified as follows: (a) male or female under or over 40 years of age; (b) disease duration according to treatment (under or over 8 years of disease); (c) classification according to fluctuating levels of IFN-γ, IL-10 and IL-17A in the following three stages of disease evolution: <5 years, between 5 and 10 years, and >10 years. Conclusion: These subgroups must be taken into account for the clinical follow-up of patients with MS in order to provide them with a better and more personalized treatment, and also for a deep and detailed analysis of progressive disease, in an attempt to comprehend fluctuations and clinical variability by means of a better understanding of intrinsically physiological variables of the disease.

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