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Biomedical subjects

Mahsa M Amoli

Publications and source records attributed to Mahsa M Amoli.

18 recordsLinked to original sources
PubMed2005

Would blockage of cytokines improve the outcome of pancreatic islet transplantation?

It has been estimated that up to 60% of pancreatic islet tissue undergoes apoptosis within the first several days post-transplantation. This strongly suggests the involvement of an inflammatory event other than alloantigen-specific immune reaction following islet transplantation which contributes to partial destruction of grafts. Inflammatory cytokines including IL-1beta, TNF-alpha and IFN-gamma are implicated in the pancreatic islet beta-cell death and functional loss during autoimmune diabetes and also seem to be involved in early loss of islet mass in islet transplantation. Inflammatory cytokines and free oxygen radicals released in situ could cause apoptosis and the functional impairment of islets after islet transplantation and graft failure. It can be hypothesized that preventing destruction of transplanted islets using cytokine blockade could be helpful in improving islet transplantation outcome. Several approaches have been made based on this hypothesis to examine the effect of inflammatory blockade on the islets survival and functional islet mass. Further investigations are required to identify most efficient way for block of cytokine-induced damage in pancreatic islets transplantation.

Animals↗
PubMed2005

Two polymorphisms in the epithelial cell-derived neutrophil-activating peptide (ENA-78) gene.

Increased expression of epithelial cell-derived neutrophil-activating peptide (ENA-78) has been reported in several immune and inflammatory conditions suggesting its role in inflammatory response. We have identified two single nucleotide polymorphisms in the promoter and exon 2 of the ENA-78 gene by scanning the full length gene using DHPLC DNA fragment analysis and DNA sequencing. The polymorphism at position +398 (A/G from the first ATG codon) in exon 2 results in a synonymous substitution not resulting in an amino acid change. The promoter polymorphism was found at position -156 (C/G from the first ATG codon). An assay was designed for the detection of the polymorphisms using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100). Allele and genotype frequencies for the promoter -156 polymorphism are presented for 107 healthy Spanish and 54 UK Caucasians. Frequencies for the exon 2 polymorphism are also presented for 63 UK Caucasians.

Chemokine CXCL5↗
PubMed2005

Lack of association between macrophage migration inhibitory factor gene polymorphism and giant cell arteritis.

OBJECTIVE: To investigate the role of macrophage migration inhibitory factor (MIF) gene polymorphism in giant cell arteritis (GCA). METHODS: Eighty-three patients with biopsy-proven GCA, 20 of them with visual ischemic complications, and 122 healthy matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for a single nucleotide polymorphism in the 5'-flanking region at position -173 of the MIF gene, using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100). RESULTS: No significant differences in MIF gene polymorphism were observed in patients with biopsy-proven GCA compared to controls. This was also the case when GCA patients with or without visual ischemic complications were compared. CONCLUSION: Polymorphism in MIF gene promoter -173 G/C does not appear to be a genetic risk factor for GCA in Northwest Spain.

Gene Frequency↗
PubMed2005

MCP-1 gene haplotype association in biopsy proven giant cell arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is the most frequent vasculitis in European and North American countries. Increased expression of monocyte chemoattractant protein 1 (MCP-1) has been observed within the inflammatory infiltrates of blood vessels and serum of patients with GCA and in other autoimmune and inflammatory conditions. MCP-1 gene polymorphisms have been reported to contribute to susceptibility to several immune and inflammatory conditions. To investigate the clinical implication of MCP-1 polymorphisms in GCA, we examined the association of 3 single nucleotide polymorphisms (SNP) in a series of patients with GCA from Northwest Spain. METHODS: Seventy-nine patients with biopsy proven GCA and 99 ethnically matched controls were studied. Patients and controls were genotyped for MCP-1 polymorphisms. SNP included in this study (rs2857657, rs4586, rs139000) were located in intron 1(G/C), exon 2(T/C), and 3'UTR(C/T) region of MCP-1 gene. RESULTS: The distribution of the alleles and genotypes for each MCP-1 polymorphism showed no significant differences between GCA patients and controls. When we compared the overall distribution of haplotype frequencies between GCA cases and controls a significant difference was observed (p = 0.005, by chi-square test from 4 2 contingency table). In addition, haplotype C-C was significantly increased in GCA patients compared with controls (p = 0.03, OR 2.09, 95% CI 1.09-4.02). Similarly, haplotype T-T was overrepresented in GCA patients (p = 0.005). CONCLUSION: Significant differences in haplotype frequencies between GCA patients and controls may indicate a role for MCP-1 gene in susceptibility to GCA.

Biopsy↗
PubMed2005

Inducible nitric oxide synthase polymorphism is associated with susceptibility to Henoch-Schönlein purpura in northwestern Spain.

OBJECTIVE: To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to the susceptibility to Henoch-Schönlein purpura (HSP), and to determine if implications exist with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction (renal sequelae). METHODS: Fifty-eight patients from Northwest Spain with primary cutaneous vasculitis classified as HSP were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls (n=251) were genotyped by PCR based techniques for a multiallelic (CCTTT)n and for the biallelic TAAA repeat in the promoter region of the NOS2A gene. RESULTS: HSP patients exhibited a significantly increased frequency of the NOS2A short (8-11) CCTTTn alleles (OR 1.64, 95% CI 1.09-2.47, p=0.017) and genotypes (OR 3.59, 95% CI 1.79-7.20, p=0.0002) compared to controls, particularly when patients with nephritis were compared with controls. However, when the NOS2A TAAA repeat polymorphism was assessed, no differences were found. CONCLUSION: Significant differences in the NOS2A promoter polymorphism allele and genotype frequency between HSP patients and controls suggest a potential role for this gene in the susceptibility to HSP and in the development of nephritis.

Follow-Up Studies↗
PubMed2004

Interleukin 1beta gene polymorphism association with severe renal manifestations and renal sequelae in Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of the interleukin (IL)-1beta gene (-511 C/T) in the incidence of Henoch-Schönlein purpura (HSP) and determine its possible implication in severe systemic complications of HSP, in particular severe renal involvement and permanent renal dysfunction (renal sequelae). METHODS: Patients from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-1beta gene (-511 C/T) polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Forty-nine Caucasian patients (38 of them younger than 21 years) who fulfilled classification criteria for HSP and 148 controls were examined. No allele or genotype differences between the whole group of HSP and controls were observed. However, all 5 patients who developed severe nephropathy during the course of disease carried the rare T allele compared with only 16 of the remaining 44 patients (pcorr = 0.01). A significant association between carriage of the -511(IL-1beta) T allele and renal sequelae (pc = 0.02; OR: 3.6, 95% CI: 1.3-10.0) was also found. CONCLUSION: In unselected patients with cutaneous vasculitis who fulfill classification criteria for HSP, carriage of IL-1beta (-511) T allele appears to influence severity of renal involvement.

Adult↗
PubMed2004

Lack of association between endothelial nitric oxide synthase polymorphisms and Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of endothelial nitric oxide synthase (eNOS) polymorphisms in the susceptibility and clinical expression of patients with cutaneous vasculitis fulfilling classification criteria for Henoch-Schönlein purpura (HSP). METHODS: Fifty patients from Northwest Spain with primary cutaneous vasculitis classified as HSP were studied. Patients and ethnically matched controls (n = 117) were genotyped by polymerase chain reaction techniques for a variable-number tandem-repeat polymorphism in intron 4, a T/C polymorphism at position -786 in the promoter region, and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. RESULTS: No differences in allele or genotype frequencies for any of the individual eNOS polymorphisms were observed between patients fulfilling HSP classification criteria and controls, or when patients were stratified for the presence of nephritis or joint or gastrointestinal manifestations. In the HSP group no linkage disequilibrium between these polymorphisms was found. No significant difference in haplotype frequencies was observed between patients and controls. CONCLUSION: Our results do not support a role for these polymorphisms in the susceptibility to HSP.

Disease Susceptibility↗
PubMed2004

Epistatic interactions between HLA-DRB1 and interleukin 4, but not interferon-gamma, increase susceptibility to giant cell arteritis.

OBJECTIVE: To assess the roles of the interleukin 4 (IL-4) and interferon-g (IFN-g) gene polymorphisms in a series of patients with biopsy-proven giant cell arteritis (GCA). METHODS: Eighty-two patients with biopsy-proven GCA and 102 ethnically matched controls from the Lugo region (Northwest Spain) were studied. The following single nucleotide polymorphisms (SNP) were assessed: IL-4 (SNP1: rs2070874, SNP2: rs2227284, SNP3: rs2227282, SNP4: rs2243266, and SNP5: rs2243267) and IFN-g (SNP1: rs1861494, SNP2: rs1861493, and SNP3: rs2069718). RESULTS: Significant differences in allele and genotype frequencies were observed for the IL-4 SNP between HLA-DRB1*04 negative patients and controls. Epistatic interaction between SNP2 (rs2227284) with HLA-DRB1 showed a significant interaction (p = 0.001) and carriage of the SNP2*T allele in the absence of HLA-DRB1*04 resulted in a 4-fold risk of developing GCA (OR 4.2, 95% CI 1.1-15.6). Also, a significant increase in the frequency of the T-T-C-A-C IL-4 haplotype was observed in HLA-DRB1*04 negative GCA patients compared to the controls (p = 0.02; OR 2.0, 95% CI 1.0-3.9). Similar distributions of allele and genotype frequencies were observed for the IFN-g polymorphisms in both GCA patients and controls. CONCLUSION: Our results suggest an association with IL-4 gene polymorphism that is dependent on HLA-DRB1 genotype in GCA susceptible individuals. These data indicate an interaction between HLA-DRB1 and IL-4 that contributes to pronounced disease susceptibility.

Adult↗
PubMed2003

Genetic markers of disease susceptibility and severity in giant cell arteritis and polymyalgia rheumatica.

BACKGROUND AND OBJECTIVES: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common and often overlapping diseases that generally occur in elderly patients. In this article, we examine the role of different genes as markers of disease susceptibility and severity in GCA and PMR. METHODS: The influence of human leukocyte antigen (HLA)-DRB1 and tumor necrosis factor alleles, as well as the different allelic polymorphisms, on the susceptibility and severity to GCA and PMR was examined. A review of the literature was conducted. RESULTS: Most studies have described an association of GCA with HLA-DRB1(*)04 alleles. However, HLA-DRB1 association in patients with PMR varies from one population to another. In Northwest Spain, patients with GCA and PMR exhibited different tumor necrosis factor microsatellite polymorphism associations. Studies of intercellular adhesion molecule-1 biallelic polymorphisms have yielded contradictory results. Interleukin 1 cluster and tumor necrosis factor alpha polymorphisms increased susceptibility to GCA and PMR slightly. In Northwest Spain, interleukin 6 promoter polymorphism at position -174 modulated the phenotypic expression of PMR in biopsy-proven GCA. In the same population, regulated upon activation, normal T cell expressed and presumably secreted gene promoter biallelic polymorphism at position -403 was a marker for PMR susceptibility but not for GCA, and corticotropin-releasing hormone polymorphism appeared to be implicated in the risk of severe ischemic complications in patients with GCA. CONCLUSIONS: The present analysis confirms that GCA and PMR are polygenic diseases. The search for additional genes is necessary to better understand the pathogenesis of these conditions.

Animals↗
PubMed2003

Corticotropin-releasing hormone promoter polymorphisms in patients with rheumatoid arthritis from northwest Spain.

OBJECTIVE: To investigate the possible implications of polymorphism in the CRH promoter in rheumatoid arthritis (RA) susceptibility, we examined a series of patients with RA from a defined area of Northwest Spain. METHODS: A total of 177 patients with RA and 147 ethnically matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for CRH polymorphisms in the 5' regulatory region of the gene at position 1273 (alleles A1 and A2) and at position 225 (alleles B1 and B2) by PCR-restriction fragment length polymorphism. Patients were stratified for age at onset of disease and rheumatoid factor status. RESULTS: When the whole group of patients was examined, no significant differences in CRH allele or genotype frequency were found compared with controls. However, the CRH allele A2 was significantly increased in patients with late onset seronegative RA compared with the seronegative group with younger age of disease onset (p = 0.03). In addition, 4 (36.4%) of the 11 patients with late onset seronegative RA carried the CRH-A2 allele versus only 2 (6.6%) of 31 patients with seronegative RA beginning before age 61 (OR 8.3, 95% CI 1.4-47.0; p = 0.015). CONCLUSION: In Northwest Spain, polymorphism in the CRH gene regulatory region may play a role as a disease susceptibility marker for late onset seronegative RA.

Age of Onset↗
PubMed2003

Endothelial nitric oxide synthase haplotype associations in biopsy-proven giant cell arteritis.

OBJECTIVE: To assess the influence of endothelial nitric oxide synthase (eNOS) polymorphisms in the susceptibility to giant cell arteritis (GCA). METHODS: We studied 57 patients with biopsy-proven GCA diagnosed at the Rheumatology Division of Hospital Xeral-Calde and 117 ethnically matched controls. Patients and controls were genotyped by PCR for a variable number tandem repeat polymorphism in intron 4, a T/C polymorphism at position -786 in the promoter region, and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. RESULTS: No differences in allele or genotype frequencies for individual polymorphisms were observed between patients with GCA and controls. However, when haplotype frequencies for the combination of the 3 eNOS polymorphisms were estimated, a significant increase in the frequency of haplotype C/1/T and a significant decrease in the frequency of haplotype C/1/G were observed in GCA patients compared to controls (p = 0.04, OR 1.8, 95% CI 1.0-3.3; p = 0.02, OR 0.3, 95% CI 0.1-0.8, respectively). CONCLUSION: Significant differences in eNOS haplotype frequencies between GCA patients and controls may indicate a role for these polymorphisms in the susceptibility to this condition.

Base Sequence↗
PubMed2002

Intercellular adhesion molecule-1 gene polymorphisms in isolated polymyalgia rheumatica.

OBJECTIVE: In untreated polymyalgia rheumatica (PMR), high levels of circulating soluble intercellular adhesion molecule-1 (ICAM-1) have been observed. To investigate the clinical implication of ICAM-1 polymorphisms in isolated PMR, we examined their potential influence in an unselected series of patients. METHODS: We studied 72 patients with isolated PMR and 129 ethnically matched controls from Lugo, Spain. Patients and controls were genotyped for HLA-DRB1 and ICAM-1 polymorphism at codons 241 and 469 by molecular methods. RESULTS: The distribution of alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between patients with isolated PMR and controls. There were also no associations between ICAM-1 polymorphisms and relapses of the disease. The latter was primarily associated with carriage of an HLA-DRB1*0401 allele (OR 7.2, p = 0.01), although all relapsed patients with HLA-DRB1*0401 also carried the GG genotype of the ICAM-1 polymorphism at codon 241. The presence of both HLA-DRB1*0401 and the GG241 ICAM-1 genotype gave an OR of 15.2 (p = 0.005) after correction for age and sex. CONCLUSION: Although ICAM-1 polymorphisms alone do not appear to be associated with disease severity in isolated PMR, the presence of both HLA-DRB1*0401 and the ICAM-1 codon 241 GG homozygosity was significantly associated with increased risk of relapses in these patients.

Gene Frequency↗
PubMed2002

Henoch-Schönlein purpura and cutaneous leukocytoclastic angiitis exhibit different HLA-DRB1 associations.

OBJECTIVE: To examine the HLA-DRB1 genotype of patients with cutaneous leukocytoclastic angiitis (CLA), a small-sized blood vessel vasculitis limited to skin, and determine if differences exist with Henoch-Schönlein purpura (HSP), a small-sized blood vessel vasculitis with cutaneous and systemic complications. METHODS: A retrospective study was performed on an unselected population of patients from Northwest Spain with primary cutaneous vasculitis classified according to proposed criteria. Patients who fulfilled classification criteria for hypersensitivity vasculitis were included in this study if they had a biopsy proven leukocytoclastic vasculitis limited to skin and, due to this, they also met the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. Patients were included in this study if they had at least 2 years' followup. We studied 96 Caucasian patients (58 HSP, 38 CLA). Patients and ethnically matched controls (n = 145) were HLA-DRB1 genotyped from DNA using molecular based methods. RESULTS: No HLA-DRB1 genotype differences between patients with CLA and controls were seen. HLA-DRB1*01 was increased and HLA-DRB1*07 reduced in HSP patients compared to controls. When HLA-DRB1 genotypes of patients with CLA and HSP were compared a significant increase of HLA-DRB1*15/16 and especially of HLA-DRB1*07 was observed in the patients fulfilling definitions for CLA compared to those with HSP. CONCLUSION: HSP and CLA exhibit different HLA-DRB1 genotype associations.

Adult↗
PubMed2002

HLA-B35 association with nephritis in Henoch-Schönlein purpura.

OBJECTIVE: To investigate the implications of the HLA-B locus in the susceptibility to Henoch-Schönlein purpura (HSP) and determine if there are associations with renal and gastrointestinal (GI) manifestations of the disease. METHODS: A retrospective study was performed on an unselected population of patients with HSP from Northwest Spain. Forty-eight Caucasian patients (24 women), 11 of them older than 20 years, were studied. Patients and ethnically matched controls were HLA-B genotyped from DNA using molecular based methods. RESULTS: When patients with HSP were compared with matched controls, no differences in HLA-B frequencies were observed. No HLA-B associations with GI manifestations were observed. In contrast, an increased frequency of HLA-B35 was observed in patients with renal manifestations (10 of 31) compared to those without (0 of 17). No significant distortions in frequency were seen for any other HLA-B alleles with HSP subgroups. CONCLUSION: Our results support a role of HLA-B35 in the susceptibility for nephritis in unselected patients with HSP.

Adult↗
PubMed2002

Interleukin 1 receptor antagonist gene polymorphism is associated with severe renal involvement and renal sequelae in Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of interleukin 1 receptor antagonist gene polymorphism (IL1RN) in the incidence of Henoch-Schönlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA) and to determine if implications exist with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction (renal sequelae). METHODS: Patients from Northwest Spain with primary cutaneous vasculitis classified as HSP or hypersensitivity vasculitis (HV) according to proposed criteria were studied. Patients with HV were included if they had a biopsy proven small size blood vessel leukocytoclastic vasculitis limited to skin and also fulfilled the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis definitions for CLA. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-1 receptor antagonist intron 2 VNTR polymorphism. RESULTS: We examined 96 Caucasian patients (58 HSP and 38 CLA) and 109 controls. No allele or genotype differences between the whole group of HSP or CLA patients and controls were observed. We found a significant association between carriage of IL-1 receptor antagonist allele 2 (ILRN*2) and severe renal involvement, manifested as nephrotic syndrome and/or renal insufficiency (p = 0.016), and permanent renal involvement (renal sequelae) (p = 0.012). CONCLUSION: In unselected patients with cutaneous vasculitis, carriage of ILRN*2 alleles influences disease severity rather than susceptibility.

Adolescent↗
PubMed2002

Macrophage migration inhibitory factor gene polymorphism is associated with sarcoidosis in biopsy proven erythema nodosum.

OBJECTIVE: To assess whether polymorphism of the macrophage migration inhibitory factor (MIF) gene at the position -173 is implicated in the development of sarcoidosis. METHODS: Twenty-eight patients with biopsy proven erythema nodosum (EN) associated with sarcoidosis, 70 patients with biopsy proven EN related to other etiologies, and 122 healthy matched controls from the Lugo region of Northwest Spain were studied. Patients and controls were genotyped for a single nucleotide polymorphism in the 5'-flanking region at position -173 of the MIF gene, using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100). RESULTS: A significantly increased frequency of the C mutant allele was observed in patients with EN secondary to sarcoidosis compared to controls (p = 0.0016; p(corr) = 0.0032; OR 2.78, 95% CI 1.45, 5.35) and also compared to patients with EN unrelated to sarcoidosis (p = 0.0004; p(corr) = 0.0008; OR 3.72, 95% CI 1.75, 7.87). Patients with EN carrying an MIF 173 C allele were found to have an increased risk of sarcoidosis (57% in EN secondary to sarcoidosis vs 24% in patients with EN related to other etiologies; p = 0.002; p(corr) = 0.004; OR 4.16, 95% CI 1.64, 10.50). CONCLUSION: This is the first attempt to assess the influence of MIF genetic polymorphism at position -173 in the development of sarcoidosis. The MIF 173 C allele is associated with a significantly increased risk of developing sarcoidosis in patients with EN.

Adolescent↗
PubMed2002

Interleukin 8 gene polymorphism is associated with increased risk of nephritis in cutaneous vasculitis.

OBJECTIVE: To assess the influence of interleukin-8 (IL-8), epithelial cell-derived neutrophil-activating peptide (ENA-78), and regulated upon activation normal T cell expressed and secreted (RANTES) gene polymorphisms in the susceptibility and clinical expression of patients fulfilling classification criteria for Henoch-Schönlein purpura (HSP). METHODS: Fifty patients (25 men) from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-8, ENA-78, and RANTES gene polymorphisms. RESULTS: No allele or genotype differences between patients fulfilling HSP classification criteria and controls were observed for any of the chemokines. However, a significantly increased frequency of allele A of the IL-8 gene polymorphism was found in patients with HSP who developed renal manifestations compared with patients without renal involvement (p = 0.02; pcorr = 0.036). Moreover, the genotype distribution in HSP patients with and without renal involvement showed statistically significant differences (p = 0.02). CONCLUSION: In unselected patients with cutaneous vasculitis, carriage of IL-8 allele A influences the susceptibility to renal involvement.

Adolescent↗