Table 4 - uploaded by Elisabet Svenungsson
Content may be subject to copyright.
Allele frequencies for the Bcl-2 SNPs in Swedish single case families. Analysis gave no significant P values
Source publication
We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in auto...
Similar publications
Objective: We have conducted the first study of the association of interleukin (IL)-10, tumor necrosis factor alpha (TNF-α), and IL23R-IL12RB2 region single nucleotide polymorphisms (SNPs) with Behçet’s disease (BD) in Western Algeria.
Methods: A total of 51 BD patients and 96 unrelated controls from West region of Algeria were genotyped by direct...
Citations
... Additionally, a full genome scan showed that the 18q21-q22 region (in which BCL2 is located) was associated with SLE. 23 However, a case-control study by Johansson et al. 24 and transmission imbalance analyses found no correlation in Mexican or Swedish SLE pedigrees, and no association was found in Caucasian 25 and Italian 26 populations. Komaki et al. 27 showed that the first SNP at codon 43 of BCL2 is an A-G polymorphism, corresponding to a novel polymorphic (Ala43Thr; ACC ! ...
... First, all of our patients were Chinese, and our findings should be interpreted while considering that association analyses of microsatellite and SNP markers did not support the involvement of BCL2 in SLE in Mexican and Swedish patients and their families. 24 Second, our patients were at different stages of disease, and some were receiving treatment drugs that may have affected gene expression. Third, our sample size was small, so our results may not be widely representative. ...
Objective:
Abnormal B cell lymphoma-2 (Bcl-2) and interleukin-19 (IL-19) expression is closely related to systemic lupus erythematosus (SLE) pathogenesis. We aimed to determine whether BCL2 polymorphisms and a single nucleotide polymorphism (SNP) of IL19 are significantly associated with SLE susceptibility and if this is affected by synergism between IL19 and BCL2 genotypes.
Methods:
This observational cohort study randomly enrolled 150 patients with SLE and 150 healthy controls. Major BCL2 and IL19 allele and genotype distributions were examined in the two groups. The IL19 SNP rs2243188 was determined using the TaqMan-MGB probe method. The synergistic effect between BCL2 and IL19 and clinical symptoms of SLE was also analyzed.
Results:
The distribution of major BCL2 genotypes and common BCL2 alleles, especially for genotypes 191, 193, and 197, differed significantly between patients and controls. A significant difference in the dominant genetic model was also observed between groups, but not in the recessive model. The risk of disease in individuals who carried both 195-bp BCL2 and 138-bp IL19 susceptibility alleles was higher than in those carrying either allele alone.
Conclusions:
This preliminary study suggested that BCL2 polymorphisms and the IL19 SNP rs2243188 are closely related to the pathogenesis of SLE.
... Thus, frequency of IL10.G9 allele (21 CA repeats) was significantly decreased in European [30] [66] [71] and Mexican-American [70] SLE patients, whereas the long alleles IL10.G10, G11 and G13 (with a CA repeat number greater than 21) were significantly increased in Mexican-American [70], Italian [30] [66] and British [71] patients respectively. On the contrary, an increase in IL10.G4 (short allele) was reported in Chinese patients [29] whereas no significant differences in IL10.G alleles were detected in other cohorts [65] [68] [72] [73]. In addition, a meta-analysis study showed only association of the IL10.G11 allele with SLE susceptibility in the populations analyzed (OR = 1.279; 95% CI: 1.027–1.593; ...
The production of two regulators of the inflammatory response, interleukin 10 (IL-10) and tumor necrosis factor
α (TNFα), has been found to be deeply deregulated in SLE patients, suggesting that these cytokines may be involved in the pathogenesis of the disease. Genetic polymorphisms at the promoter regions of IL-10 and TNFα genes have been associated with different constitutive and induced cytokine production. Given that individual steady-state levels of these molecules may deviate an initial immune response towards different forms of lymphocyte activation, functional genetic variants in their promoters could influence the development of SLE. The present review summarizes the information previously reported about the involvement of IL-10 and TNFα genetic variants on SLE appearance, clinical phenotype, and outcome. We show that, in spite of the heterogeneity of the populations studied, the existing knowledge points towards a relevant role of IL-10 and TNFα genotypes in SLE.
... gene and consisting, for both, in A /G transition as previously described (Tanaka et al., 1991; Johansson et al., 2000). The SNP-52, at position +52 of transcription start site, is within the coding region but is non-synonymous (does not result in amino acid substitution). ...
Many studies have shown linkage between IDDM6 locus on 18q12-q21 chromosome and several autoimmune diseases, suggesting that it might harbour susceptibility genes common to autoimmunity. Using 12 families deriving from a large Tunisian multiplex family (the Akr family) from which 38 people were affected with autoimmune thyroid diseases (AITD), and 193 unrelated AITD patients, tested against 100 healthy subjects, we tried to replicate the positive results previously reported for the IDDM6. Akr members were genotyped with eight microsatellite markers harbouring the IDDM6 region. Multipoint non-parametric linkage analysis have shown a clear peak values of NPL score around D18S41 marker (Z = 3.72, P = 0.0001). Family-based association test (FBAT) and transmission disequilibrium test (TDT) have confirmed linkage results. In particular, a significant association with allele 3 of D18S41 and allele 2 of D18S57 markers was found. Case-control studies, using one intragenic microsatellite (locus CTG18.1) marker in the immunoglobulin transcription factor (ITF2) gene, a 5' flanking AC repeat of the anti-apoptotic BCL-2 gene as well as two SNPs at positions +52 and +1955 from transcription start site of BCL-2, showed no significant association between neither genes and AITD. Our study is the first replication of the 18q12-q21 chromosome region as a potential candidate to AITD genetic susceptibility. The Akr family has shown evidence for linkage between IDDM6 locus and AITD. Moreover, case-control study does not support the involvement of ITF2 and BCL2 genes in AITD pathogenesis.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoantibody production and immune complex formation whose deposition causes chronic inflammatory lesions in different organs.1,2 Mechanisms that contribute to the formation of auto-antibodies and immune complexes include loss of tolerance to nuclear antigens and other components of one’s own body, decreased clearance of immune complexes, and abnormal B- and T-cell activation.² The disease is characterized by a combination of different clinical and immunological symptoms reported in Table 18.1.
Background:
Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the disruption of the immune homeostasis. Patients exhibit a wide range of clinical manifestations, and environmental and genetic factors are involved in SLE pathogenesis. Evidence suggests that abnormalities in the cellular and molecular events that coordinate apoptosis may favour the generation of autoantigens involved in autoimmunity. In this way, the apoptotic deregulation may be affected by polymorphic variants in apoptotic-related genes.
Methods:
We analyzed FAS, FASL, BCL-2 and BAX polymorphisms in order to correlate to SLE susceptibility and clinical features. A total of 427 SLE patients from the Hospital de Clínicas de Porto Alegre and 543 controls from southern Brazil were evaluated.
Results:
We observed higher frequencies of the FASL -844CC genotype and -844C allele, as well as of the FASL-844C/IVS2nt-124A haplotype in African-derived SLE patients when compared to controls (P < 0.001). FASL -844C, which is related to high FasL expression, could contribute to increased apoptosis and to the breakdown of immunological tolerance, favouring autoantibody production and inflammation. On the other hand, the BAX -248GA genotype and the -248A allele, related to low protein expression, were observed as a protective factor against SLE in this same population. The rate of apoptosis and cell death was evaluated in peripheral lymphocytes, and SLE patients presented a higher percentage of dead lymphocytes (CD3(+)Annexin V(+) 7-AAD(+)) compared to the control group.
Conclusion:
Our data support a role for apoptosis in SLE susceptibility.
The actual cause of systemic lupus erythematosus (SLE) is unknown. This chapter reviews the genetic basis for SLE, the familial aggregation in SLE, the current status of genome-wide scans in families of SLE patients, organization of the MHC, the association of MHC genes and susceptibility to SLE, and the autoantibody subsets of SLE and their MHC class II associations. Family and twin studies clearly have established the importance of genetic factors in SLE, and studies of HLA class II and III genes have underscored their consistent associations with disease in nearly all ethnic groups, the contribution of non-MHC genes to SLE predisposition, clinical and autoantibody subsets, and course and prognosis are only being determined currently. Studies defining associations with non-MHC genes and linkage studies of multiplex families from several centers have raised as many new questions as they have answered. Inadequate power from small sample sizes and family collections, stemming undoubtedly from the clinical heterogeneity posed by SLE in no small part, has caused this. However, as the family collections continue, data are pooled and reanalyzed, and clinical subsets of SLE further considered, definitive candidate genes should emerge beyond perhaps the three that have withstood time and reconfirmation in different groups of patients: the MHC, the FCγ genes, and whatever disease-relevant gene found in the region on chromosome q41-42. This results in better insights into the immunologic perturbations that set the stage for SLE, which will in turn allow novel approaches to therapy.
The main objective of the current study is to examine the role of the statistical relation between BCL2 gene (Ala43Thr) single nucleotide polymorphism and growth hormone (GH1) levels in Egyptian HCV genotype-4 patients before and after treatment with pegylated interferon plus ribavirin. Eighty patients with HCV genotype-4 and 40 healthy volunteers as controls were enrolled in the prospective study. Gene polymorphism of BCL2 (Ala43Thr) using PCR-RFLP technique and GH1 concentrations using ELISA procedure were measured for all patients and controls. The present study resulted that Responder HCV genotype-4 Patients, with BCL2 43Ala genotype, have high significant increase in pre-treatment GH1 levels (>1 ng/ml); which represent normal levels, as compared to non-responders pre-treatment GH1 levels (<1 ng/ml); which represent low concentrations. We concluded that HCV genotype-4 patients who have normal GH1 concentrations and BCL-2 43Ala genotype can successfully achieve response to interferon based therapy.
Alberto Mantovani – Istituto de Ricerche Farmacologiche Mario Negri, Milan, Italy
Diamond and colleagues review the complexity of the pathogenesis of systemic lupus erythmatosus (SLE), a systemic autoimmune disorder. Genetic background is an important element in determining susceptibility to the disease and there are many triggering factors that aggravate it including ultraviolet light, certain drugs, hormones and possibly infectious agents. The article summarizes the pathogenic events that characterize SLE. The authors have made widely recognized contributions to the understanding of the pathogenesis of autoimmunity.
