Altered suppressor function of regulatoryT cells in type 1 diabetes

Background: Type 1 diabetes [T1D] is a T cell mediated autoimmune disease targetingthe insulin-producing beta cells within pancreatic islets. Autoimmune diseases maydevelop as a consequence of altered balance between regulatory [Tregs] andautoreactive T cells

Objectives: To evaluate Treg cells frequency and suppressivefunction in the peripheral blood of newly diagnosed T1D patients in comparison withhealthy controls

Methods: Fifteen new cases of T1D patients and 15 age- and sexmatchedhealthy controls were recruited to this study. Their peripheral bloodmononuclear cells [PBMCs] were isolated and CD4[+]CD25[+]FoxP3[+]CD127[-/low] Treg cellswere studied by flowcytometry technique. Thereafter, Tregs were isolated by Magnetic-Activated Cell Separation [MACS] technology and by using CFSE [carboxyfluoresceinsuccinimidyl ester] dilution assay, their suppressive activity was evaluated in thecoculture of CD4[+]CD25[-] T responder cells with Treg cells

Results: The percentage ofCD4[+]CD25[+]FoxP3[+]CD127[-/low] Tregs did not differ between T1D patients and healthycontrols but the MFI [mean fluorescence intensity] of transcription factor FoxP3[forkhead box protein P3] was significantly decreased in T1D patients [20.03 +/- 1.4 vs.31.33 +/- 2.95, p=0.0017]. Moreover, the suppressive function of CD4[+]CD25[+]CD127[-/low]Treg cells was significantly diminished in T1D patients in comparison with controlgroup [35.16 +/- 4.93% vs. 60.45 +/- 5.26%, respectively, p=0.0015]

Conclusion: Presentstudy indicates an impaired immune regulation among T1D patients, characterized bydefects in suppressive function and expression of FoxP3 in Treg cells without anysignificant decrease in their frequency in peripheral blood

role of cytomegalovirus haemophilus influenzae and epstein barr virus in guillain barre syndrome

Guillain Barre Syndrome [GBS] is an inflammatory, usually demyelinating, polyneuropathy; clinically characterized by acute onset of symmetric progressive muscle weakness with loss of myotatic reflexes. Thirty five patients with GBS, defined clinically according to the criteria of Asbury and Cornblath, were recruited from three hospital affiliated to Tehran University of Medical Sciences. Controls: As a control group 35 age and sex matched patients with other neurological diseases admitted to the same hospital at the same time, were included in our study. Serum samples were collected before treatment from each patient [within 4 weeks after the disease onset] and controls, and stored frozen at -80°C until serologic assays were done. Serologic testing of pretreatment serum was performed in all patients. Positive titer of virus specific IgM antibody against cytomegalovirus [CMV] was found in 6 cases and 2 controls. 34 patients and 31 controls had high titer of anti Haemophilus influenzae IgG and one patient had serologic evidence of a recent Epstein Barr virus [EBV] infection. The mean titer of IgG antibody against Haemophilus influenzae in cases and controls was 5.21 and 2.97 respectively. Although serologic evidence of all these infections were more frequent in cases than in controls, only Haemophilus influenzae infection appeared to be significantly related to GBS [P=0.002]. Eleven cases and 3 controls had high titers of IgG antibody against Haemophilus influenzae type B [titer >8]. There is significant association between high titer of IgG antibody against Haemophilus influenzae and GBS [MX017]. Our results provide further evidence that Haemophilus influenzae and probably CMV, can be associated with GBS

Association between HLA-DQB1[asterisk]03:01 and Bullous pemphigoid in Iranian patients

A common Human Leukocyte Antigen [HLA] class II allele, DQ beta 1[asterisk]03:01, seems to be associated with Bullous pemphigoid [BP] in Caucasians whereas previous studies in other ethnic groups showed other HLA class II alleles as genetic predisposing factors for BP. To investigate the association of HLA class II alleles and haplotypes with BP in Iranian population. Methods: Fifty patients with Bullous pemphigoid and 180 geographically matched, healthy individuals as control group enrolled into this study. HLA typing of class II [DR and DQ alleles] was carried out using polymerase chain reaction based on sequence-specific primers method. Class II DQA1 and DQB1 typing showed a significantly higher frequency of HLA-DQA1[asterisk]05:01 [45% vs. 33%, p=0.03], HLA-DQB1[asterisk]03:01 [36% vs. 23.6%, p=0.02] and HLA-DQB1[asterisk]04:01 [4% vs. 1.6%, p=0.04] in the BP patients compared with controls. For DRB1 allele frequencies, there were no significant disease associations. The frequency of DRB1[asterisk]08:01/DQA1[asterisk]05:01/DQB1[asterisk]03:01 [3% vs. 0%, p=0.02] haplotype showed an increase among patients compared with controls. Our data suggest that Iranian patients with BP present the same genetic predisposition linked to HLA-DQB1[asterisk]03:01 previously reported in Caucasians

Expression, purification and characterization of three overlapping immunodominant recombinant fragments from Bordetella pertussis filamentous hemagglutinin

Filamentous hemagglutinin [FHA] is one of the most important immunoprotective antigens of Bordetella pertussis [B. pertussis] and a major component of the acellular pertussis vaccine. In the present study, three overlapping recombinant fragments from the immunodominant region of FHA were produced and their immunogenicity was investigated. Three overlapping coding sequences of FHA antigen were amplified from B. pertussis genomic DNA by PCR. Amplified fragments were expressed in Escherichia coli [E. coli] BL21[DE3] strain and purified through His-tag using Nickel-based chromatography. Purified fragments were characterized by SDS-PAGE and Western blotting techniques. In vitro peripheral blood mononuclear cells [PBMC] proliferation and IFN- gamma production were assessed in a limited number of healthy adults vaccinated with a commercial acellular pertussis vaccine in response to all purified FHA fragments by H3-Thymidine incorporation and ELISA, respectively. Recombinant FHA segments were successfully cloned and produced at high levels in E. coli BL21[DE3]. SDS-PAGE and Western blot analyses confirmed their purity and reactivity. All three recombinant fragments together with a commercial native FHA were able to induce in vitro PBMC proliferation and IFN- gamma production. Our preliminary results suggest that these overlapping recombinant FHA fragments are immunogenic and may prove to be immunoprotective

Diagnostic value of interferon-gamma assay in tuberculosis pericardial effusions: study on a cohort of Iranian patients

Tuberculosis pericarditis as a potentially fatal complication of tuberculosis requires effective diagnosis and treatment. We evaluated the efficacy of interferon-gamma [IFN-gamma] and adenosine deaminase [ADA] for diagnosing tuberculosis pericarditis in a cohort of Iranian patients presenting with pericarditis. We enrolled 38 patients with presentation of pericarditis. All patients underwent diagnostic and therapeutic pericardiostomy with drainage and biopsy. Adenosine deaminase and interferon-gamma levels were determined in pericardial fluid samples of all patients. Pericardial tissue samples were submitted for histopathologic and microbiologic studies. Polymerase chain reaction [PCR] was performed on all pericardial fluid samples to detect Mycobacterium tuberculosis. From 38 patients with pericarditis, 7 cases were diagnosed as having tuberculosis pericarditis [18.4%]. Mean concentration of interferon-gamma in tuberculosis group was significantly higher compared to non-tuberculosis group [69257 pg/l [range: 26600-148000] vs. 329 pg/l [range: 0-2200], P<0.000]. Receiver operating characteristic [ROC] curve showed a value of 14400 pg/l as the cutoff point with a sensitivity of 100% and specificity of 100% for diagnosing tuberculosis pericardial effusion. Adenosine deaminase was not found to be significantly higher in tuberculosis group in comparison with non-tuberculosis causes of pericardial effusion [35.7 [range: 9-69] vs. 36.03 [range: 8-420], P=0.28]. In this study interferon-gamma showed to be a valuable diagnostic test for detection of tuberculosis pericarditis among a cohort of Iranian patients. We suggest using interferon-gamma to diagnose tuberculosis pericarditis to make diagnose in case of suspicion. While in this study, adenosine deaminase measurement did not prove to have the characteristics of an accurate diagnostic test for tuberculosis pericarditis

Association of HLA-DRB1, DQA1 and DQB1 alleles and haplotypes with common variable immunodeficiency in iranian patients

Common Variable Immunodeficiency [CVID] is an antibody deficiency syndrome that often co-occurs in families with selective IgA deficiency [IgAD]. This study was designed to investigate the frequency of DR and DQ loci of HLA class II region in common variable immunodeficiency [CVID] patients. Fifteen Iranian patients with CVID or IgAD [mean age 14.6 +/- 5.4, range 4-25 years; 9 male and 6 female] and 63 healthy controls were studied. Establishment of B-lymphoblastoid cell lines was performed using Epstein-Barr-virus [EBV] immortalization technique and HLA alleles were typed using polymerase chain reaction based on sequence specific primers [PCR-SSP]. DRB1 alleles including DRB1 *04 [p=0.03] and DRB1 *11 [p=0.01] significantly showed higher frequency in the studied subjects. In contrast, DRB1 *301 [p=0.04] and DRB1 *07 [p=0.02] alleles were negatively associated with CVID. For DQB1 and DQA1 loci, DQB1 *0302 [p=0.047] and DQA1 *03011 [p=0.001] demon-strated high frequency in cases, while DQB1 *0201 [p=0.02] and DQA1 *0201 [p=0.01] were detected to be low when compared to controls. Haplotype analysis indicated that frequency of DRB1*04-DQB1*03011-DQA1 *03011 [p=0.02], DRB1 *11-DQB1 *03011-DQA1 *0505 [p=0.047], DRB1 *11-DQA1 *0505 [p=0.04] and DRB1*04-DQA1*03011 [p=0.02] haplotypes were significantly higher in patient group, while only the frequency of the DRB1 *07-DQA1 *0201 haplotype gene was statistically lower in control group [p=0.02]. According to the results, it could be deduced that the HLA-DR and DQ loci may contribute to the pathogenesis of CVID or they might be considered as suitable markers for the possibility of the occurrence of this genetic defect

Lack of association between interleukin 12 C[-1188]A polymorphism and irritable bowel syndrome

Irritable Bowel Syndrome [IBS] is a functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. This study was performed to investigate the important role of interleukin-12 [IL-12] in intestinal inflammation. For this study seventy one patients with IBS and 140 controls were investigated. The allele and genotype frequencies of IL-12 C[-1188]A were determined using polymerase chain reaction with sequence-specific primers. The allele A was more common that the allele C in both groups of patients and controls. There was not any significant difference on IL-12 alleles and genotypes between patients and controls. The AA genotype was the most common genotypes, which was seen in 57.4% of the patients and 51.4% of the controls [p=0.53]. Although frequency of the CC genotype in the control group was lower than the patient group, this difference was not significant [5.7% vs. 11.5%, respectively, p=0.16]. Considering the lack of association between IL-12 C[-1188]A polymorphism and IBS, this cytokine gene polymorphism may not have significant role in the pathophysiology of disease

High frequency of clinically significant infections and cytomegalovirus disease in kidney transplant recipients with serum mannose-binding lectin deficiency

Mannose-binding lectin [MBL] constitutes defense against infections when adaptive immune response is compromised. Elevation in serum MBL levels has been shown in patients with kidney failure. We compared serum MBL levels before and after kidney transplant and evaluated association of MBL deficiency with infectious complications in kidney transplant recipients. This study was performed in 71 kidney transplant recipients and 48 healthy controls. In 36 recipients [group 1], serum MBL levels were tested before and on days 7 and 14 after transplantation. They were followed up for 6 months. In 35 recipients [group 2], serum MBL was measured during their posttransplant follow-up visits. In both groups, frequencies of clinically significant infections and acute rejection were compared between those with low MBL [< 500 ng/mL] and normal/high MBL [< 500 ng/mL]. Serum MBL levels [1744 +/- 905 ng/mL] were not higher in group 1 before transplantation than in controls. One and 2 weeks after transplantation, MBL levels decreased to 1699 +/- 1030 ng/mL and 1562 +/- 1020 ng/mL, respectively. Five patients who had low serum MBL levels experienced more frequent episodes of infections [P = .008] and CMV disease [P < .001]. Ten patients in group 2 with low MBL levels had more frequent episodes of CMV disease [P = .01]. These findings suggest a potential role for MBL in defense against developing posttransplant CMV disease and that low serum MBL levels in kidney transplant recipients be considered an indicator of the need for CMV prophylaxis

Desmoglein ELISA in the diagnosis of pemphigus and its correlation with the severity of pemphigus vulgaris

Anti-desmoglein 3 and 1 autoantibodies are involved in the pathogenesis of pemphigus diseases. Our objective was to assess the value of ELISA in the diagnosis of pemphigus and its correlation with the severity of pemphigus vulgaris. Based on clinical presentation and histopathologic confirmation for the diagnosis of the pemphigus, 38 patients took part in the study. Sera of the patients were tested by desmoglein 1 and desmoglein 3 ELISA. Also, direct immunofluorescence was performed for all patients which revealed positive results in 36 patients [94.7%]. ELISA was positive in 37 of 38 pemphigus patients [Sensitivity: 97.3%]. The relationship between desmoglein 1 index values and skin severity was statistically significant [p<0.05]. Desmoglein 3 index values increased with oral severity although this was not statistically significant. Iranian patients similar to Indian patients had higher positive anti-desmoglein 1 autoantibodies. Desmoglein-ELISA test is appropriate in the diagnosis of pemphigus. Desmoglein 1 index value is statistically correlated with the severity of pemphigus vulgaris

Human leukocyte antigens [HLA] associated with selective IgA deficiency in Iran and Sweden

Selective IgA deficiency [IgAD] [serum IgA concentration of <0.07 g/l] is the most common primary immunodeficiency in Caucasians, with an estimated prevalence of 1/600. There are strong indications for involvement of genetic factors in development of the disease and the frequency of several extended major histocompatibility complex haplotypes [including HLA-A1, B8, DR3, DQ2] have previously been shown to be increased among Caucasian patients with IgAD. PCR was used to type HLA B, DR, and DQ alleles in 29 Iranian individuals with IgAD and 299 Swedish individuals with IgAD. The results indicate a strong association with the HLA B14, DR1 alleles in Iranian subjects and HLA B8, B12, B13, B14, B40, DR1, DR3, DR7, DQ2 and DQ5 alleles in Swedish subjects. Differences in HLA association of IgAD in Iran and Sweden confirm the notion of a genetic background of the disease and that multiple, potentially different genes within the MHC region might be involved in the pathogenesis of IgAD in different ethnic groups

Association of HLA class II alleles with childhood asthma and total IgE levels

Asthma is a complex and multifactorial disorder. Several studies have reported association between different HLA- DQB1 and HLA- DRB1 alleles and allergic asthma. The aim of the present study was to investigate the association of HLA-class II alleles and haplotypes, with total serum IgE and the results of the skin prick test in Iranian children with allergic asthma. A total of 112 patients with allergic asthma symptoms [75 males and 37 females] were selected randomly from the pediatric hospital. In some patients total serum IgE and prick test were determined. Data of this study shows that HLA-DRB1*12 significantly increased in asthmatic patients [4.5% vs. 0%, P-value=0.04]. HLA-DQB1*0603 and 0604 alleles were significantly higher in asthmatics than those in normal controls [10% vs. 0%, P-value= 0.0001; and 9.3% vs. 3.7%, P-value= 0.04, respectively]. The statistical significance was relinquished after p value correction for all alleles except for HLA-DQB1*0602 [Pc=0.03] and HLA-DQB1*0603 [Pc=0.0015]. Conversely, HLA-DQB1*0501 and 0602 were decreased in asthmatics compared to normal controls [7.5% vs. 13.5%, P-value= 0.05; and 4% vs. 12.5%, P-value= 0.002, respectively]. The mean of total IgE in patients was 483 IU, and it was significantly high about 1140 IU in asthmatic patients with positive skin prick test to house dust. The most frequent alleles in asthmatic patients with the total IgE>200 IU/mL were HLA-DRB1*11and 1401, HLA-DQA1*0505, HLA-DQB1*0301 and in patients with total IgE<200 IU/mL were HLA-DRB1*0301, 07 and 1301, HLADQA1*0201 and 0301, HLA-DQB1*0201. These data suggests that HLA-DRB1, DQA1 and DQB1 alleles and haplotypes might be implicated in susceptibility to allergy and asthma and serum IgE production. As asthma and atopy are multifactorial disorders, probably HLA genes are involved in the regulation of immune specific responses to common allergen

B-cell lineage study in patients with juvenile idiopathic arthritis

Juvenile idiopathic arthritis [JIA] is the most common rheumatic disease in children. The exact causes of disease are still poorly understood. It seems that B cells have several functions in JIA, including production of autoantibodies, antigen presentation, production of cytokines, and activation of T cells. Here, we aimed to evaluate B-cell lineage and its precursors in the bone marrow of patients with JIA Twenty consecutive patients with JIA were enrolled in this study. JIA is subdivided into three groups of Pauciarticular, Polyarticular, and Systemic JIA. Bone marrow mononuclear cells were separated. Then we analyzed the immunophenotype of the JIA patients by flow cytometry. After separation, the mononuclear cells were stained specific for B cell lineage [CD10, CD19 and CD20], T cell lineage [CD3] and non specific lineage [CD34, HLA-DR and TdT]. Flow cytometric study of bone marrow showed that JIA patients had low level of CD10, CD19, and CD20.Polyarticular patients had lower level of D10, CD19, and CD20 than pauciarticular JIA patients and systemic onset JIA patients had lower levels than both of them. Decreasing of B cell precursor in bone marrow is one of mechanisms for pathogenesis of JIA and the more decreased B cell precursors in bone marrow are, the worst severity of the disease is. Significant differences in CD10 content of bone marrow were detected between the polyarticular and pauciarticular groups. So, it seems that polyarticular JIA patients had lower percentage of pre B cell stage

HLA-DRB1, DQA1 and DQB1 alleles and haplotypes frequencies in Iranian healthy adult responders and non-responders to recombinant hepatitis B vaccine

Different studies have demonstrated that a small proportion of healthy individuals receiving the hepatitis B [HB] vaccine do not produce protective levels of anti-HB antibody, a phenomenon which could be linked to certain human leukocyte antigen [HLA] class-II alleles or haplotypes. The present study was undertaken to determine the frequency of HLA class-II alleles in Iranian healthy adult responders and non-responders to HB vaccine. Twelve non-responders [anti-HBs antibody < 10 IU/L] and 46 responders [anti-HBs antibody > 100 IU/L] were tissue typed for HLA class-II. HLA-DRB1, DQB1 and DQA1 alleles were determined using polymerase chain reaction based on sequence specific primers [PCR-SSP] technique. Accessibility to excess amount of genomic DNA was possible using Epstein-Barr virus [EBV]-transformed B-cells established from all vaccinees. Our results demonstrated increased frequencies of HLA- DRB1*07, DRB1*03, DRB1*04, DQB1*0201, DQA1*0201 alleles and HLA- DRB1*07/DQB1*0201/DQA1*0201 and DRB1*04/DQB1*0302/DQA1*03011 haplotypes in the non-responder group. Comparison between responders and non-responders revealed only a significant difference for DQB1*0201 allele [p < 0.05]. These findings confirm the association of certain HLA alleles and haplotypes with the lack of antibody response to HB vaccine in an Iranian population

Determination of HLA-B27 subtypes in Iranian patients with ankylosing spondylitis

The human leukocyte antigen-B27 is one of the class I molecules of the major histocompatibility complex which is strongly associated with ankylosing spondylitis [AS]. The strength of the disease association with B27 varies markedly among racial and ethnic populations. It is an allele family, which constitutes about 31 subtypes, with a considerable geographic and ethnic difference in distribution. It is important to know whether certain subtypes show any preferential association with AS. Because there is no report regarding HLA-B27 subtypes in Iranian patients with AS, main purpose of the present study was to assess the frequency of subtypes of human leukocyte antigen [HLA]-B27 in patients with ankylosing spondylitis in Iranian population One hundred and nineteen AS patients [82 HLA-B27 positive and 37 HLA-B27 negative] were selected for this study. HLA-B27 positive patients were by polymerase chain reaction amplification with sequence-specific primers [PCR-SSP] for B 27 subtyping. The results of present study revealed that only two subtypes were detected in Iranian patients, including B 2705 [52 patients, 63.4%] and B 2702 [30 patients, 36.6%]. Our results showed a restricted number of HLA-B27 subtypes associated with AS in Iran and an elevated frequency of the B 2705 allele in these patients similar to other Euro-Caucasoid [Aryan] groups in the world

IL-1, IL-1R and TNFalpha gene polymorphisms in Iranian patients with multiple sclerosis

Different research groups have extensively studied the associations of cytokine gene polymorphisms in different diseases. The role of cytokines gene polymorphisms in multiple sclerosis [MS], as a chronic Immune-mediated neurodegenerative disease, has been previously reported in the various populations. For determining pro-inflammatory cytokine gene polymorphisms, 100 relapsing remitting multiple sclerosis [RRMS] Iranian patients and 140 normal individuals as control enrolled in this study. DNA of each sample was extracted by a modified salting out method. Cytokine single gene nucleotide polymorphisms including IL-1alpha -889, IL-1beta [-511 and +3962], IL-1R pst1 1970, IL-1RA mspal 11100, and TNF-alpha [-308 and -238] were determined by using the PCR-SSP method. The results of our data indicate the decrease in frequency of IL-1alpha TC-889 genotype [p=0.002], IL-1beta TC +3962 genotype [p=0.004], IL-1R T pst1 1970 allele [p= 0.0001], IL-1 RA TC Mspa1 11100 genotype [p=0.009], TNF-alpha A-308 allele [p=0.0002] and AG genotype [p=0.00001] in the patients group versus normal subjects. On the other hand the frequency of IL-1alpha TT -889 genotype [p=0.028], IL-1R C pst1 1970 allele [p=0.0001] and CC genotype [p=0.00006], TNFalpha G -308 allele [p=0.0002] and GG genotype [p=0.000001] decreased significantly in the patients versus normal subjects. These results suggest that polymorphic variations of these pro-inflammatory cytokines may play an important role in susceptibility of Iranian multiple sclerosis patients

Presence of idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia in the patients with common variable immunodeficiency

Common Variable Immunodeficiency [CVID] is a heterogeneous group of disorders characterized by hypogammaglobulinemia and an increased susceptibility to recurrent infections as well as autoimmunity and malignancies. Idiopathic Thrombocytopenic Purpura [ITP] and Autoimmune Hemolytic Anemia [AIHA] are two autoimmune disorders which may be seen in association with CVID. Among 85 CVID patients, seven cases had ITP and/or AIHA [8%]. Four of these patients had one or more episodes of ITP, one patient had AIHA, and two patients had both ITP and AIHA [Evans syndrome]. Almost, all patients experienced chronic and recurrent infections mostly in respiratory and gastrointestinal systems during the course of the disease. Among the seven patients, five presented their underlying disease with recurrent respiratory and/or gastrointestinal tract infections, while in two remaining patients, CVID was presented with ITP. Three patients died until now; two because of hepatic failure and one due to pulmonary hemorrhage. As CVID is prone to autoimmune disorders, it should be considered as a differential diagnosis of adult-onset ITP and possibly in children. Chronic and recurrent ITP, especially in the presence of propensity to respiratory and gastrointestinal infections mandate the evaluation for an underlying immune dysregulation such as CVID

Human leukocyte antigen profile of two ethnic groups in southeast of Iran

This study was performed to determine the genetic diversity of HLA class I and II alleles among two ethnic groups in Southeastern Iran. HLA profiles were determined in 71 Iranian populations [41 Zaboli and 30 Baloch]. The frequencies of HLA-A02 [p=0.017],-Cw4 [p=0.003], and-DR8 [p=0.025] in the Zaboli populations were significantly higher than that in Baloch ethnic group. In contrast, the frequency of HLA-A23 allele was more frequent in Baloch than Zaboli [p=0.020]. This report represents an important resource for investigators in the fields of transplantation immunology and population genetics from widely dispersed areas of Iran

Angiotensin Converting Enzyme Gene polymorphism in Iranian Patients with Type 2 Diabetes

Angiotensin I converting enzyme [ACE] is a Zinc metalloproteinase, converts Ang I to Ang- IIa pro-inflammatory agent which may contribute to pathophysiology of some diseases like type 2 diabetes. To investigate the relationship between ACE I/D polymorphism and type 2 diabetes in 261 Iranian casecontrol pairs. 170 patients [85 type 2 diabetics with nephropathy and 85 type 2 diabetics without nephropathy] and 91 healthy control subjects were enrolled in our study. I/D polymorphism of the ACE gene was detected by polymerase chain reaction [PCR] utilizing specific primers. The frequency of DD genotype in the DN group was higher than that of the type 2 diabetic patients [30.6% vs. 20%, P = 0.157] and the control group [30.6% vs. 14.3%, P=0.006]. The frequency of D allele in nephropathic patients was 58.2% as compared to type 2 diabetic patients without nephropathy 50.5% [P=0.19] and control subjects 37.3% [P =0.001]. Therefore, the frequency of DD genotype and D allele significantly increased in DN patients in comparison to healthy controls. It is concluded that the DD genotype and /or D allele of ACE gene may increase the risk for type 2 diabetes but not diabetic nephropathy

Cytokine gene polymorphisms in iranian patients with beta-thalassemia major

beta-thalassemia as a hereditary disease is defined as defective synthesis of beta -globin chains, resulting in erythropoiesis abnormalities and severe anemia. Different studies have shown that cytokines and cytokine gene polymorphisms play a major role in the pathogenesis of beta -thalassemia. Single nucleotide polymorphisms [SNPs] within the promoter region or other regulatory sequences of cytokine genes lead to overall production of cytokines. To analyze the genetic profile of Thl and Th2 cytokines in Iranian patients with beta -thalassemia major. Allelic and genotype frequencies of cytokine genes were determined in 30 thalassemia patients and 40 healthy subjects using PCR-SSP assay. Allele and genotype frequencies were calculated and compared with those of normal controls. The results of our study show a significant decrease in A allele at position UTR 5644 IFN-y, G alleles at position -238 TNF-oc and 166 IL-2, and C allele at position -590 IL-4. TGF- beta haplotype TG/TG increased whereas TGF- beta haplotype CG/CG and IL-10 haplotype GCC/ACC decreased significantly in all patients. Data of this investigation suggest that variations among cytokine gene polymorphisms may contribute to the disease susceptibility. A finding which needs to be fairly clarified in other ethnic groups