Nora Magdalena 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

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.

Lack of Association of the Polymorphisms IL-17A (-197G/A) and IL-17F (+7488A/G) with Multibacillary Leprosy in Mexican Patients.

Background. Leprosy is a chronic infectious disease caused by the intracellular acid-fast bacilli Mycobacterium leprae; it has been determined that genetic factors of the host play an important role in the disease susceptibility. Thus, in this case-control study, we evaluated the possible association between the IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs and susceptibility to leprosy disease in Mexican population. Methods. Seventy-five leprosy patients and sixty-nine control subjects were included. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique. Results. We found nonsignificant differences in genotype and allele frequencies related to IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs in MB as well as subclinical forms of leprosy disease versus healthy individuals. Conclusions. Since the sample size is not large enough, it is difficult to sustain an association of susceptibility to leprosy with genotypes or allele frequencies of IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780), suggesting that IL-17 polymorphisms have no significant role in the genetic susceptibility to development of this disease in the Mexican Mestizo population.

MIF functional polymorphisms (-794 CATT 5-8 and -173 G>C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population

Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT5-8MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population.

PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_89∗G, PADI4_90∗T and PADI4_92∗G gene polymorphisms were associated with RA susceptibility (OR=1.34, p=0.04; OR=1.35, p=0.03; OR=1.34, p=0.04; respectively). The GTG haplotype was also significantly associated with RA (OR=2.27 95%CI=1.18-4.41; p=0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.

Association of extrapituitary prolactin promoter polymorphism with disease susceptibility and anti-RNP antibodies in Mexican patients with systemic lupus erythematosus

Introduction Prolactin (PRL) is a 23-kDa protein that can be synthesized and secreted by pituitary and extrapituitary tissues such as immune cells due to its expression being regulated by two independent promoter regions. The promoter which is responsible for extrapituitary expression contains the single nucleotide polymorphism (SNP) –1149 G/T previously associated with autoimmune diseases in various populations. This study evaluates the relationship of PRL –1149 G/T polymorphism with PRL serum levels and clinical characteristics in systemic lupus erythematosus (SLE) patients from western Mexico. Material and methods One hundred and sixty-three SLE patients classified according to the 1982 American College of Rheumatology (ACR) SLE classification criteria and 326 unrelated control subjects (CS), both from western Mexico, were included. The PRL –1149 G/T polymorphism was genotyped using the polymerase chain reaction restriction fragment length polymorphism technique, and both PRL serum levels and autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA). Results We found an association between the PRL –1149 TT genotype and SLE according to the recessive genetic model (OR = 2.26, 95% CI: 1.01–5.08, p = 0.04). The TT genotype was associated with anti-RNP antibodies (p = 0.04) and with higher scores of the Mex-SLEDAI (p = 0.02). Moreover, SLE patients showed elevated PRL serum levels (12.4 ng/ml; p < 0.01), and this condition was associated with renal activity and the presence of anti-RNP antibodies. Conclusions PRL –1149 TT genotype is associated with susceptibility to SLE in a Mexican-Mestizo population, and high PRL serum levels are associated with anti-RNP antibodies and renal activity.