Lack of association between the polymorphism at the heat-shock protein (HSP70-2) gene and systemic lupus erythematosus (SLE) in the Mexican Mestizo population (original) (raw)
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Lupus, 1996
Alleles of the major histocompatibility complex (MHC) have been recognized as genetic factors for the development of SLE. The [HLA-B8; SC01; DR3] extended haplotype seems to be relevant in patients from white European descent, pertinent alleles, however, are diffi cult to select on haplotypes with linkage disequilibrium. Studies in non-Caucasian patients are therefore mandatory. Admixture estimates in Mexicans have shown a proportion of 56% of Indian genes, 40% of Caucasian genes and from 4 to 12% of Black genes. In order to determine the relevant MHC loci in the genetic susceptibility for SLE we studied Class I, II and III alleles in 102 Mexican SLE patients and 350 of their first degree relatives and compared these two groups to another one composed by 200 ethnically matched normal individuals. We found significantly increased frequencies of HLA-DR3 (pC = 0.03, RR = 2.56) and DR7 (pC = 0.004, RR = 3.08) in SLE patients as compared to controls. On the other hand, first degree relat...
HLA class II haplotypes in Mexican systemic lupus erythematosus patients
Human Immunology, 2004
Systemic lupus erythematosus (SLE) is an autoimmune disease in which polymorphisms within the human leukocyte antigen (HLA) region have been associated to its etiology. For this study, HLA-DQB1, DQA1, and DRB1 genes were typed by polymerase chain reactionsequence-specific primer in 237 individuals, taken from 74 families, who had a member with SLE, and who had their residence in the western region of Mexico; as well as in 159 ethnically matched healthy volunteers taken from 32 families. Genotype and allele frequency analysis was performed in 74 SLE patients and 54 unrelated controls. Precise threeloci identification of independent haplotypes was performed in 48 patients and 54 controls by familial segregation. Genotype distribution at each loci was concordant with Hardy-Weinberg's equilibrium in the control group. In general, no genotype effect was observed in SLE patients.
Human Immunology, 2001
The aim of the present study was to determine the relevant major histocompatibility complex (MHC) class II alleles in the genetic susceptibility to systemic lupus erythematosus (SLE) in Mexican Mestizo patients. We examined the gene and haplotype frequencies of the HLA-DRB1, DQA1 and DQB1 alleles by polymerase chain reaction-sequence-specific oligonucleotide probes in 81 Mexican SLE Mestizo patients and 99 ethnically matched controls. We found a significantly increased frequency of the HLA-DRB1*0301 (p(c) = 0.031, odds ratio = 2.63) allele and significantly decreased frequencies of the DRB1*0802 (p(c) = 0.035) and DRB1*1101 (p(c) = 0.037) alleles in the SLE group. Haplotype analysis showed increased frequencies of DRB1*0301-DQA1*0501-DQB1*0201 (p(c) = 0.017, odds ratio = 2.97), and decreased frequency of DRB1*0802-DQA1*0401-DQB1*0402 (p(c) = 0.034) in SLE patients. The most frequently detected haplotypes in SLE patients showed different haplotypic combinations in the homologous chromosome from those found in controls. Thus, the combinations detected in SLE patients were either not detected in the control group or infrequently found. The results suggest that the DRB1*0301 is the principal class II allele associated with the genetic susceptibility to SLE in Mexican patients and that the presence of a specific haplotype of the homologous chromosome in patients with DRB1*0407-DQA1*03-DQB1*0302 and DRB1*1501-DQA1*0102-DQB1*0602 haplotypes could have an additive effect on the susceptibility to the disease. Finally, the low frequency of the DRB1*0301 and DRB1*1501 alleles in the control population suggests that the genetic admixture between Mexican Indians and Caucasian populations was an event that could have increased the risk of Mexicans to develop SLE.
Journal of the Selva Andina Research Society, 2020
La susceptibilidad individual en autoinmunidad puede estar determinada por una combinación de polimorfismos específicos de genes que codifican para múltiples proteínas, citoquinas, antígenos del complejo principal de histocompatibilidad, moléculas de adhesión, y proteínas celulares. Esta condición puede conducir a la expresión anormal de moléculas inmunoreguladoras y finalmente resultar en el desarrollo o exacerbación de la enfermedad autoinmune. HLA-G es una molécula glicoprotéica del MHC de clase I, la cual cumple con funciones muy importante al momento de activar y regular el sistema inmune. Por lo tanto, lo que se pretende con este estudio es determinar la asociación genética entre el polimorfismo de 14 pb del gen HLA-G con la susceptibilidad a contraer LES y las manifestaciones clínicas de la enfermedad. La población de estudio consistió de 120 pacientes con LES y 112 pacientes sin la enfermedad (grupo control), 94% procedía de la ciudad de La Paz, quienes asistieron al Instituto SELADIS. Para el estudio se obtuvo el DNA humano a partir de sangre periférica, se realizó la PCR para la tipificación molecular de los genotipos y alelos que fueron revelados por medio de electroforesis en gel de agarosa. Al mismo tiempo se realizaron pruebas serológicas por ELISA para determinar la presencia de anticuerpos IgG anti-DNA de doble cadena en los pacientes lúpicos. Los resultados de la PCR mostraron que los pacientes lúpicos tienen mayor frecuencia de expresión del genotipo Ins/Del (OR=1.72, p<0.05); mientras que, la presencia del genotipo homocigoto Ins/Ins es más frecuente en el grupo control (OR=0.29, p<0.001), mostrándose de esta forma que el primer genotipo es un factor de riesgo y el segundo, un factor de protección a padecer LES respectivamente. Se observó también que entre pacientes y controles no existe diferencia significativa en la frecuencia de presentación del genotipo Del/Del en homocigosis. En cuanto a las frecuencias alélicas se obtuvo que el alelo deleción en más frecuente en el grupo de pacientes lúpicos, a comparación del grupo control donde ambos alelos presentaron el mismo porcentaje. Con respecto a las manifestaciones clínicas se observó que el polimorfismo Ins/Del (O.R=8.64) es factor de riesgo para el desarrollo de manifestaciones dermatológicas. 2020. Journal of the Selva Andina Research Society®. Bolivia. Todos los derechos reservados.
Tissue antigens, 2015
This study aims to comprehensively analyze human leucocyte antigen (HLA)-G polymorphisms association with susceptibility to systemic lupus erythematosus (SLE) development and clinical manifestations. The HLA-G 5' upstream regulatory region (URR), 3' untranslated region (UTR) and a cytosine deletion at exon 3 (ΔC, HLA-G*0105N allele) were analyzed in 114 SLE patients and 128 healthy controls from North East Brazil. The +3003T>C (rs1707) C allele and the HG010101c extended HLA-G allele were significantly more frequent in SLE patients than healthy controls (+3003C allele frequency: 12% in SLE patients vs 6% in controls; odds ratio (OR), 2.10, 95% confidence interval (CI), 1.06-4.28, P = 0.026; HG010101c frequency: 11.8% in SLE patients and 6.3% in controls; OR, 2.14, 95% CI, 1.01-4.51, P = 0.046) and were associated with susceptibility for disease development. Other polymorphisms were associated with different clinical manifestations. Although HLA-G role in SLE disease is fa...
HLA in Portuguese Systemic Lupus Erythematosus Patients and Their Relation to Clinical Features
Annals of The New York Academy of Sciences, 2009
Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease translating the different genetic and environmental factors involved. Polymorphisms at several loci, including the major histocompatibility complex (MHC), have been associated worldwide with SLE, although inconsistencies exist among these studies mainly due to genetic heterogeneity between populations and sample characteristics. The aim of the present study was to investigate in Portuguese SLE the association of HLA-DRB1 alleles with clinical patterns of the disease and severity. Two hundred eighteen Portuguese patients with SLE—42% of whom had kidney involvement—were studied for HLA-DRB1. Clinical and laboratory manifestations were correlated with HLA allele frequencies. HLA-DRB1 * 03 allele frequency was significantly higher in SLE patients—as a whole and as either with or without renal involvement—compared to controls, while HLA-DRB1 * 09 and DRB1 * 13 allele frequencies were decreased. Regarding the relationship with the presence or absence of specific clinical manifestations, it was only found that HLA-DRB1 * 08 allele frequency was increased in patients with neurological involvement. No association with the presence or absence of anti-dsDNA, anti-sm or antiphospholipid antibodies, or antiphospholipid syndrome, was observed. These results were reproducible when analysis was repeated only with patients with more than 5 years of evolution. As in other populations HLA-DRB1 * 03 is a susceptibility allele in Portuguese SLE patients, while HLA-DRB1 * 09 and DRB1 * 13 alleles may be protective alleles, not only for the disease, but for the development of nephritis. No correlations with the different clinical manifestations were found, except with the neurological system.
The Journal of Rheumatology, 2013
Objective.HLA-G has well recognized tolerogenic properties in physiological and nonphysiological conditions. The 3′ untranslated region (3′UTR) of the HLA-G gene has at least 3 polymorphic sites (14-bpINS/DEL, +3142C/G, and +3196C/G) described as associated with posttranscriptional influence on messenger RNA production; however, only the 14-bpINS/DEL and +3142C/G sites have been studied in systemic lupus erythematosus (SLE).Methods.We investigated the HLA-G 3′UTR polymorphic sites (14-bpINS/DEL, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G, and +3196C/G) in 190 Brazilian patients with SLE and 282 healthy individuals in allele, genotype, and haplotype analyses. A multiple logistic regression model was used to assess the association of the disease features with the HLA-G 3′UTR haplotypes.Results.Increased frequencies were observed of the 14-bpINS (p = 0.053), +3010C (p = 0.008), +3142G (p = 0.006), and +3187A (p = 0.013) alleles, and increased frequencies of the 14-bpINS...
International Journal of Health Sciences, 2014
Background: Systemic lupus erythematosus (SLE) is a disease with diverse clinical presentations due to interaction between genetic and environmental factors. SLE is associated worldwide with polymorphisms at various loci, including the major histocompatibility complex (MHC), although inconsistencies exist among these studies. Aims: This study was carried out to investigate, the association of HLA-DRB1, DRB3, DRB4, DRB5, and DQB1 alleles in SLE patients and clinical presentations at Qassim, Saudi Arabia. Methods: Fifty one patients with SLE-84.3% of whom had kidney involvement were studied in a case control study for HLA-DRB1, DRB3, DRB4, DRB5, and DQB1. Results: It was found that DRB3 is a protective gene among Saudi's against SLE, HLA DRB3, HLA DRB1*11 frequency was increased in patients with serositis with a p value of (0.004), (0.047) respectively, increased frequency of HLA DQB1*3 among SLE patients with skin manifestations with a p value of (0.041), the frequency of HLA DRB1*15 alleles was increased among SLE patients with nephritis with a p value of (0.029), the frequency of HLA DRB1*11 among those with hematological manifestations with a p value of (0.03) and the frequency DRB1*10 was found to be increased among SLE patients with neurological manifestations with a p value of (0.002) Conclusion: In contradistinction to what have been found among other populations DRB3 is a protective gene among Saudi's against SLE. No evidence for a role of the HLA-DRB1, DRB4, DRB5, DQB1 alleles. There was an increased HLA DRB3 frequency with serositis, DQB1*3 skin manifestations, HLA DRB1*15 with nephritis, DRB1*10 with hematological manifestations and DRB1*11 with neurological manifestations.
HLA Class II DNA Typing in a Large Series of European Patients with Systemic Lupus Erythematosus
Medicine, 2002
The etiopathogenesis of systemic lupus erythematosus (SLE) is complex and still largely unknown. Genetic, environmental, and hormonal factors contribute to disease susceptibility (1). The importance of genetic factors is documented by 1) the pronounced difference in concordance rates between monozygotic and dizygotic twins (15); 2) the higher disease prevalence in relatives of patients with SLE (14); 3) the higher prevalence of SLE in certain ethnic groups, like African Americans and some Native Americans (18); and 4) studies of murine SLE showing that some strains invariably develop the disease (23, 24). In humans, several genes contribute to lupus susceptibility. Their identification has been complicated by the fact that SLE is a heterogeneous disease, both clinically and immunologically (3); in addition, many of the susceptibility genes differ across the various populations (27), and it is well recognized that genetic
Autoimmunity Reviews, 2008
Objective: To estimate the common effect size of HLA-DRB1 and -DQB1 alleles on systemic lupus erythematosus (SLE) susceptibility across Latin America populations through a meta-analysis. Methods: Case-control studies on HLA class II association with SLE in Latin America were searched up to August 2007. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by means of the random effect model. Results: Eleven studies were selected, which included 747 cases and 1180 controls. Associations with SLE susceptibility were found for HLA-DR2 (OR: 1.75; 95% CI: 1.40-2.19) and -DR3 (OR: 2.02; 95% CI: 1.44-2.83) groups. HLA-DRB1⁎0301 allele disclosed the strongest association (OR: 2.14; 95% CI: 1.28-3.56). HLA-DR3-DQ2 haplotype was a risk factor (OR: 2.92; 95% CI: 1.66-5.14). A protective effect was found for the HLA-DR5 group (OR: 0.43; 95% CI: 0.27-0.67), mainly due to a negative association between HLA-DRB1⁎1101 allele and disease (OR: 0.21; 95% CI: 0.06-0.72). Functional analysis of susceptibility and protective alleles revealed physicochemical differences of critical amino acids shaping the peptide-binding groove at DRβ chain allowing us to infer an approach to understand the role of HLA in SLE. No significant association was established for HLA-DQB1 alleles. Conclusions: HLA-DRB1 gene is a mayor factor for development of SLE in Latin Americans.