Significant associations of the rs3104413 single-nucleotide polymorphism in the hla region with type 1 diabetes

Background and Aims: In this study, the effect of rs310441 polymorphism in the human leukocyte antigen [HLA] region on the development of susceptibility or resistance to Type 1 diabetes [T1D] among the people with T1D compared to healthy subjects has been investigated

Materials and Methods: This research, which is based on the examination of 130 cases with T1D and 98 controls, has been carried out in the city of Hamedan after clinical examination. In order to determine the HLA gene polymorphism, the allele-specific-refractory mutation system-polymerase chain reaction [ARMS-PCR] method was utilized

Results: This study indicated that there is a significant relationship between the frequency of alleles and genotypes in the patients compared to healthy subjects. The C/C and C/G genotypes were more frequent in patients than controls and G/G genotype was shown to be protective for T1D [p=0.01]. Significant difference was found for the G allelic frequency in patients with T1D and in the control group. The allelic frequency was significantly different between the two groups [p=0.0001]. Our findings indicate that HLA polymorphism[C/G] and [C/C] genotypes could be considered as genetic risk factors associated with susceptibility and [G/G] genotypes associated with protection for T1D

Conclusions: This study identified that there is a significant relationship between the frequency of alleles and genotypes in the patients compared to healthy subjects

Evaluation of interleukin 8 +2767 A/T polymorphism in visceral leishmaniasis

OBJECTIVE@#To evaluated the relationship between the genetic variations at IL-8 +2767 position with VL pathogenesis among Iranian patients.@*METHODS@#Three groups including patients with VL clinical presentation and leishmania seropositive (n = 124), patients seropositive but without clinical presentation (n = 82) and healthy controls (n = 63) were selected to conduct this cross-sectional study. Polymorphism at +2767 position of IL-8 was investigated using PCR-RFLP techniques. Anti-leishmania antibody titration was evaluated by the immunoflorescence technique.@*RESULTS@#We observed higher significant frequencies +2767 A/A and A/T genotypes in Group 1 compared to Group 2 and healthy controls (P = 0.001). Also, patients in Group 1 carrying A/A genotype showed higher titer of anti-leishmania antibody than patients with A/T and T/T genotypes (P = 0.05). The validity of the data was analyzed using Hardy-Weinberg equilibrium and one way analysis of variance (ANOVA), as well as χ tests.@*CONCLUSIONS@#Our findings indicate that the IL-8 +2767 polymorphism is significantly involved in impaired immune responses against VL and it could be considered as a risk factor for the VL progress.

Evaluation of interleukin 8 +2767 A/T polymorphism in visceral leishmaniasis

Objective To evaluated the relationship between the genetic variations at IL-8 +2767 position with VL pathogenesis among Iranian patients. Methods Three groups including patients with VL clinical presentation and leishmania seropositive (n = 124), patients seropositive but without clinical presentation (n = 82) and healthy controls (n = 63) were selected to conduct this cross-sectional study. Polymorphism at +2767 position of IL-8 was investigated using PCR-RFLP techniques. Anti-leishmania antibody titration was evaluated by the immunoflorescence technique. Results We observed higher significant frequencies +2767 A/A and A/T genotypes in Group 1 compared to Group 2 and healthy controls (P = 0.001). Also, patients in Group 1 carrying A/A genotype showed higher titer of anti-leishmania antibody than patients with A/T and T/T genotypes (P = 0.05). The validity of the data was analyzed using Hardy–Weinberg equilibrium and one way analysis of variance (ANOVA), as well as χ

HLA-KIR interactions and immunity to viral infections

Host genetic factors play a central role in determining the clinical phenotype of human diseases. Association between two polymorphic loci in human genome, human leukocyte antigen [HLA] and killer cell immunoglobulin-like receptors [KIRs], and genetically complex infectious disease, particularly those of viral etiology, have been historically elusive. Hence, defining the influence of genetic diversity in HLA and KIRs on the outcome of viral infections has been extensively started in clinically well-defined cohort studies. HLA genes encode molecules which present antigenic peptide fragments to T lymphocytes as central players in adaptive immunity against infectious diseases. KIRs are expressed on natural killer cells which perform a crucial role in innate immunity to pathogen infection. The effector functions of NK cells such as direct killing of infected cells, cytokine production, and cross-talk with adaptive immune system depend on activation of NK cells, which is determined by their surface receptors. Among these receptors, KIRs, which interact with HLA class I, are mainly inhibitory and exhibit substantial genetic diversity. An extensive body of association studies indicates a role for HLA-KIRs interactions in infectious diseases, autoimmune disorders, cancer, transplantation, and reproduction. Various compound HLA-KIR genotypes appear to affect outcome of viral infections that suggests a role for HLA class I diversity in innate immunity as well as adaptive immune responses. The aim of this review is focusing on the impact of HLA and KIR alleles and different combinations of these alleles on clinical outcome of viral diseases to validate this proof-of-concept with respect to the therapeutic interventions

L-selectin Phe206Leu gene polymorphism is not associated with visceral leishmaniasis

Previous studies revealed that selectins play key roles in homing of immune cells to inflamed tissues and lymphatic organs. L-selectins are expressed on immune cells and interact with P and E selectins to homing to the tissues, hence, the polymorphisms within the gene of L-selectins may are associated with alteration in its expression. Thus, the current cross-sectional analytical study has been designed to investigate the polymorphisms within L-selectin gene and their relation with visceral leishmaniasis [VL]. This study was performed on 194 samples during 2004-2012.The PCR-SSP and immunoflorescence techniques were used to evaluate the L-selectins polymorphism and anti-Leishmaniaantibody titration, respectively, in 56, 74 and 64 seropositive VL patients [group 1], seropositive healthy controls [group 2] and seronegative healthy controls [group 3]. The results showed that the genotypes [P=0.711] and alleles [P=0.679] within L-selectins gene [A/C] was not differ between groups. Our results also demonstrated that the genotypes within L-selectins in group 1 [P=0.807] and 2 [P=0.441] were not associated with the titration of anti-leishmania antibody. The results identified that the polymorphisms within L-selectins gene were not associated with VL and it may be concluded that these genotypes and alleles are unable to affect immune responses in VL patients

Is the polymorphism at position -1082 of IL-10 gene associated with visceral leishmaniasis?

Immune responses play critical roles in the leishmaniasis eradication. IL-10 is a key regulator of immune responses, and the polymorphisms within its promoter region are associated with alteration in its expression. Therefore, this study was designed to examine the correlation between polymorphism at the -1082 position of the IL-10 gene and visceral leishmaniasis [VL]. The IL-10 -1082 polymorphism and anti-Leishmania antibody titration were examined in 110 patients with clinical presentation of VL and seropositive for the Leishmania [group 1], 74 seropositive patients but without clinical presentation [group 2] and 113 healthy controls [group 3] using the PCR-RFLP and immunofluorescence techniques, respectively. The polymorphism at IL-10 -1082 [A/G] position was significantly associated with VL and A/G genotype was significantly higher in VL patients when compared to the groups 2 and 3 [P< 0.001]. However, the results demonstrated that the A and G alleles were not associated with VL [P= 0.263]. Previous investigations have shown that the polymorphism at the -1082 position of the IL-10 gene can influence its expression and also it has been proved that IL-10 level was increased during VL. Our results suggest that the A/G genotype may be considered as a risk factor for VL

Evaluation of fibronectin and c-reactive protein levels in patients with sepsis: a case-control study

Sepsis is a significant health problem with an estimated 750,000 new cases in the USA annually. It is also the third leading cause of death in developed countries, equaling the number of fatalities from acute myocardial infarction. The high sepsis-related mortalities mean there is an urgent need to improve the diagnosis and management of sepsis patients. The aim of this study was the evaluation of fibronectin and C-reactive protein [CRP] plasma levels in patients with sepsis and other infectious diseases without sepsis. In a case-control study, 90 patients with sepsis and 90 patients with other infectious diseases without sepsis were studied. Serum levels of fibronectin and CRP were measured. The data were analyzed by SPSS version 15. The mean levels of fibronectin in the cases and controls were 288.97 +/- 89.10 mg/l and 341.24 +/- 110.53 mg/l respectively [P=0.001]. The mean levels of CRP in the cases and controls were 89.42 +/- 54.05 micro g/ml and 27.42 +/- 25.89 micro g/ml respectively [P<0.001]. Concerning the source of infection, the mean CRP levels were significantly higher in septic patients with urinary tract infection, pneumonia, and soft tissue infection [P<0.001]. Decreased levels of fibronectin and increased levels of CRP may be considered as reliable diagnostic markers for sepsis. Also, CRP could be a better predictive factor for sepsis than fibronectin

Relationship between Helicobacter pylori infection and chronic obstructive pulmonary disease

There is some evidence indicating the role of Helicobacter pylori infection in pathogenesis of extragastrointestinal diseases including skin, vascular, and autoimmune disorders, as well as some respiratory diseases. The aim of this study was to investigate the association between H. pylori and chronic obstructive pulmonary disease [COPD]. In a case-control study, 90 patients with COPD and 90 age-and sex-matched control subjects were included. Serum samples were tested for anti-H. pylori and anti-CagA IgG by ELISA. A physician completed a questionnaire including demographic characteristics, habitual history, and spirometric findings for each patient. Of 90 patients with COPD 66 [51%] had mild, 31 [34.4%] moderate, and 13 [14.4%] sever disease. There was no significant association between H. pylori IgG seropositivity and COPD. Serum levels of anti-CagA IgG were significantly higher in patients with COPD than in the control subjects [P<0.001]. No association was observed between H. pylori infection and severity of COPD. The results suggest that there is an association between CagA-positive H. pylori infections and COPD. Further studies should be planned to investigate the potential pathogenic mechanisms that might underlie these associations

Onychomadesis in a patient with immunoglobulin class switch recombination deficiency

Immunoglobulin class switch recombination deficiencies [Ig CSR deficiencies] or Hyper IgM syndromes [HIGM] are a group of primary immunodeficiency diseases, characterized by defective CD40 signaling of B cells resulting into a CSR and a somatic hypermutation. The affected patients are characterized with reduced serum levels of IgG and IgA, and normal or elevated level of IgM, which lead to increased susceptibility to infections. We describe a 3 year-old boy with frequent bacterial infections of the skin and respiratory tract, mucosal ulcers, and diarrhea. He experienced onychomadesis in both fingernails and toenails during recent bacterial infection. Quantitative immunoglobulin levels revealed high levels of serum IgM and very low levels of IgG, IgA, and IgE. Clinical and immunologic studies supported the diagnosis of HIGM. Onychomadesis as a finding in HIGM could be considered. Considering exclusion of CD40L, CD40, AID and UNG genes by molecular analysis, new CSR selective deficiencies could be suspected in this case

E-selectin S128R polymorphism leads to severe asthma

The E-selectin mediates the interaction of activated endothelial cells with leukocytes and plays a fundamental role in the pathogenesis of asthma. It has been suggested that an S/R [Serine128 Arginine] polymorphism of E-selectin alters ligand binding function. Our purpose in this study was to determine whether this Serine128 Arginine polymorphism influences the risk of asthma and also to analyze the possible correlation of disease severity in Iranian patients with polymorphism of E-selectin. We studied human E-selectin gene polymorphism in 172 asthmatic patients and 173 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]. To determine the severity of the asthma's situation, a questionnaire was prepared requesting the following information: age, sex, clinical signs and symptoms and past medical history. After the participants filled in the questionnaire, all active or ex-smoker patients were excluded. A trained observer assessed airway reversibility, peak flowmetry and spirometry in asthmatic patients. We found increased serum levels of soluble E-selectin [sE-selectin] in asthmatic patients compared with healthy subjects [P <0.0001]. Frequencies of the SS, SR, and RR genotypes were found as 66.3%, 31.4%, and 2.3% in the patients and 91.9%, 8.1%, and 0.0% in control subjects, respectively. The 128 Arg allele was more prevalent in patients than controls [OR 5.78; 95% CI, 3.07-10.86, P<0.0001]. However, in this study the polymorphism was not associated with circulating sE-selectin levels. We found a direct correlation between the level of sE-selectin and the severity of asthma [P=0.001]. On the other hand, there was a close relation between 128 Arginine carriage and disease severity [P<0.0001]. These results suggest that the Ser 128 Arg polymorphism of the E-selectin gene is a genetic factor that may be associated with the severity of asthma