Prevalence of blaCTX-M Gene among Extended-Spectrum ß-Lactamases Producing Klebsiella pneumoniae Clinical Isolates in Iran: A Meta-Analysis.

BACKGROUND: CTX-M-type extended-spectrum ß-lactamases (ESBLs) are the most prevalent ESBLs in bacterial members of Enterobacteriaceae family including Klebsiella pneumoniae. The global spread of CTX-M-producing K. pneumoniae is a major concern in most countries including Iran. The aim of this meta-analysis was to determine the relative frequency (RF) of blaCTX-M gene among ESBLs-producing K. pneumoniae clinical isolates in Iran and to report an overall prevalence. METHODS: A comprehensive literature search of studies published up to July 2016 was carried out. The keywords "Enterobacteriaceae", "Klebsiella pneumoniae", "ESBLs", "CTX-M" and "Iran" were searched in PubMed, Scopus, EBSCO, Google Scholar, Scirus, SID and IranMedex in both English and Persian. Selected articles were published between July 2010 and July 2016 and all of them were in English. STATA SE version 11.0 was used for statistical analysis. RESULTS: Twenty-four articles/abstracts were included in this analysis. Selected studies were performed in Ahvaz, Arak, Ilam, Kashan, Kerman, Mashhad, Shiraz, Tabriz, Tehran, Zabol, and Zahedan. Our pooled evidence showed that the RF of blaCTX-M gene among ESBLs-producing K. pneumoniae clinical isolates varied from 7.7% in Tabriz to 100% in Mashhad, Tehran, and Zahedan, with an overall RF of 56.7%. CONCLUSION: Our meta-analysis revealed that the RF of CTX-M-type ESBLs-producing K. pneumoniae is diverse in different regions of Iran, and the central and eastern regions had higher prevalence rates compared to western regions.

Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats.

BACKGROUND: Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress, hepatocellular injury and fibrosis. Quercetin is a flavonoid with antifibrotic, and hepatoprotective properties. However, the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood. The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model. METHODS: We divided male Wistar rats into 4 groups (n=8 for each): sham, sham+quercetin (30 mg/kg per day), BDL, and BDL+quercetin (30 mg/kg per day). Four weeks later, the rats were sacrificed, the blood was collected for liver enzyme measurements and liver for the measurement of Rac1, Rac1-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting, respectively. RESULTS: Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes. Furthermore, the mRNA and protein expression of Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (P<0.05); quercetin treatment reversed these variables back toward normal (P<0.05). Another interesting finding was that the antioxidant markers e.g. superoxide dismutase and catalase were elevated in quercetin-treated BDL rats compared to BDL rats (P<0.05). CONCLUSION: Quercetin demonstrated hepatoprotective activity against BDL-induced liver injury through increasing antioxidant capacity of the liver tissue, while preventing the production of Rac1, Rac1-GTP and NOX1 proteins.

Meta-analysis: the relationship between CTLA-4 +49 A/G polymorphism and primary biliary cirrhosis and type I autoimmune hepatitis.

OBJECTIVES: CTLA-4 exon-1 +49A > G (rs231775) polymorphism has been reported to influence the risk for primary biliary cirrhosis (PBC) as well as type I autoimmune hepatitis (AIH-1) in many studies; however, the results still remain controversial and ambiguous. This study aimed to determine more precise estimations for the relationship between CTLA-4 +49 A > G polymorphism and the risk for PBC and AIH-1 by using a meta-analysis. DESIGN AND METHODS: PubMed, EMBASE and MEDLINE were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association. RESULTS: Fifteen studies including 3661 patients with PBC and 4427 controls as well as seven studies including 1270 patients with AIH-1 and 1614 controls were identified. Our pooled analysis revealed that G allele of CTLA-4 gene +49A/G polymorphism may confer an increased risk of PBC in overall (p = 0.001, OR = 1.29; 95% CI = 1.13-1.47) and Caucasians (p = 0.001, OR = 1.32; 95% CI = 1.21-1.44). At genotypic level, the codominant, dominant and recessive models showed no significant association with PBC. With respect to AIH-1, the AG genotype demonstrated a trend for association with increased risk of AIH-1 (p = 0.04, AG vs. AA, OR = 1.20; 95% CI = 1.01-1.43). However, the CTLA-4 alleles as well as genotypes in dominant and recessive models were not associated with a risk for AIH-1 in both Caucasians and Asians. CONCLUSIONS: This meta-analysis concluded that the CTLA-4 G allele and the AG genotype were associated with an increased risk for PBC and AIH-1, respectively, suggesting the CTLA-4 +49 A/G polymorphism as a candidate of susceptibility locus to PBC and AIH-1.

A functional polymorphism in the miR-146a gene is associated with the risk of childhood acute lymphoblastic leukemia: a preliminary report.

Growing evidence showed that microRNAs (miRs) are involved in normal hematopoiesis and the pathogenesis of several hematological malignancies. Genetic variations or mutations occurring in the miR gene region may affect the property of miRs through altering miR expression and/or maturation. The aim of the present study was to evaluate the possible relationship between two miRs polymorphisms, hsa-miR-146a (rs2910164 G>C) and hsa-miR-499 (rs3746444 T>C), and the susceptibility to childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population. This case-control study was performed on 75 children diagnosed with ALL and 115 age- and sex-matched children with no history of cancer of any type (as the control group). Tetra-primer amplification refractory mutation system-polymerase chain reaction was applied for genotyping the variants. We found that the rs2910164 G>C variant of hsa-miR-146a significantly increased the risk of ALL (CC vs. GG, OR = 4.24, 95% CI = 1.52-11.87, P = 0.006; GC vs. GG, OR = 3.55, 95% CI = 1.41-8.93, P = 0.007; C vs. T, OR = 1.73, 95% CI = 1.13-2.67, P = 0.012). With respect to hsa-miR-499 rs3746444 T/C, no significant difference in allele and genotype frequencies of the rs3746444 variant between ALL patients and controls was observed. Our results for the first time demonstrated that the miR-146a rs2910164, but not miR-499 rs3746444 variant, was associated with increased risk for developing pediatrics ALL in an Iranian population.

Investigation of CTLA-4 and CD86 gene polymorphisms in Iranian patients with brucellosis infection.

The protective immune response against Brucella involves T-cell-mediated immunity. T-lymphocyte receptors, CD28 and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), bind the same ligands, CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells and regulate T cell activation. CD28 delivers stimulatory signals whereas CTLA-4 provides inhibitory signals for T cell activation. Here, we investigated the association of four polymorphisms in CTLA4 (+49A/G [rs231775] and -318 C/T [rs5742909]) and its ligand CD86 (+1057 G/A [rs1129055] and +2379G/C [rs17281995]) with brucellosis infection. The study included 153 Iranian patients with active brucellosis and 128 healthy individuals as the control group. Genotyping of the CTLA4 and CD86 variants was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and PCR-restriction fragment length polymorphism analysis, respectively. It was found that the CTLA4 -318 CT genotype and T allele were present more frequently in cases than in controls and are therefore associated with an increased risk for brucellosis (-318 TT genotype; OR = 2.544, P = 0.002). Likewise, the CD86 +1057 GA and AA genotypes and A allele were associated with an increased risk of brucellosis (+1057 AA genotype; OR = 3.81, P = 0.001). However, no statistically significant difference between brucellosis patients and controls in the allele and genotype distributions of CTLA4, +49A/G (P = 0.859) and CD86, +2379G/C (P = 0.476) was found. In conclusion, CTLA4 -318 CT genotype and T allele and the CD86 +057 GA and AA genotypes and A allele play roles as risk factors for developing brucellosis infection in Iran.

Relationship between γ-interferon gene polymorphisms and susceptibility to brucellosis infection.

Interferon-gamma (IFN-γ) is a pro-inflammatory cytokine that plays a pivotal role in the defense mechanism against Brucella infection. It was hypothesized that the IFN-γ in (+874 A/T in intron 1) TT and +5644 T/A, TT genotypes, which are reportedly associated with high IFN production, are associated with susceptibility to brucellosis in Iranian subjects. Genotyping of these IFN-γ variants by an allele-specific polymerase chain reaction method was performed in 281 subjects, comprising 153 patients with active brucellosis and 128 healthy controls. It was found that the +874 minor allele (A) and homozygote genotype (AA) were significantly more frequently present in brucellosis patients than in controls (OR = 2.588; 95% CI, 1.313-5.104; P = 0.006 for the AA genotype; OR = 1.575; 95% CI, 1.124-2.216; P = 0.010 for the A allele). However, the allelic and genotypic distribution of the IFN-γ polymorphism at position UTR5644 A>T did not differ significantly between patients and controls (P > 0.05). The distribution of haplotypes in this study suggests that the T/A haplotype (+874/UTR5644), which was present more frequently in controls than in patients, may protect subjects against Brucella infection. It is suggested that IFN-γ +874 AA genotype and A allele are risk factors for developing brucellosis infection in Iranian subjects.

Circulating levels of interleukin (IL)-12 and IL-13 in Helicobacter pylori-infected patients, and their associations with bacterial CagA and VacA virulence factors.

OBJECTIVE: The aim of this study was to determine the association of the Helicobacter pylori virulence factors, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) antibodies, with serum levels of interleukin (IL)-12 and IL-13 in H. pylori-infected duodenal ulcer (DU) patients and H. pylori-infected asymptomatic (AS) carriers in order to elucidate any correlation between them. METHODS: A total of 67 DU patients, 48 AS individuals, and 26 healthy H. pylori-negative subjects were enrolled in this study. Serum concentrations of IL-12 and IL-13 were determined by enzyme-linked immunosorbent assay (ELISA) method. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial virulence antigens p120 (CagA) and p95 (VacA). Serum concentrations of IL-12 and IL-13 were compared in 9 groups, including 4 AS phenotypes (CagA⁺VacA⁺, CagA⁺VacA⁻, CagA⁻VacA⁺, CagA⁻VacA⁻), 4 DU phenotypes (CagA⁺VacA⁺, CagA⁺VacA⁻, CagA⁻VacA⁺, CagA⁻VacA⁻), and 1 control group. RESULTS: The results revealed that DU patients positive for CagA, independent of the anti-VacA antibody status, showed drastically elevated levels of IL-12 (251 ± 43 pg/ml) when compared with the other groups (p = 0.0001). No significant difference was found between groups regarding levels of IL-13 (p > 0.05). CONCLUSIONS: Our findings indicate that in the DU group, the serum concentrations of IL-12 but not of IL-13 were influenced by bacterial CagA, independent of the VacA status, suggesting that high IL-12 levels may contribute to susceptibility to DU in CagA-positive individuals. These findings could possibly be considered to improve the predictive or prognostic values of inflammatory cytokines for DU, and also to design possible novel therapeutic approaches.

The association of interleukin-18 promoter polymorphisms and serum levels with duodenal ulcer, and their correlations with bacterial CagA and VacA virulence factors.

BACKGROUND: We analyzed the impact of interleukin (IL)-18 promoter polymorphisms on IL-18 serum levels in Helicobacter pylori-infected duodenal ulcer (DU) patients and healthy asymptomatic (AS) carriers. We also aimed to determine the association of the H. pylori virulence factors CagA and VacA antibodies with serum concentrations of IL-18 in order to elucidate any correlation between them. METHODS: Three groups of patients were enrolled: DU patients (67 individuals), AS carriers (48 individuals), and H. pylori-negative subjects (26 individuals). Serum concentrations of IL-18 were determined by ELISA. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial CagA and VacA. Genotyping of IL-18 promoter polymorphisms at positions - 137G/C and - 607C/A were performed by allele-specific primer PCR protocol. RESULTS: Our study revealed that serum IL-18 levels are positively influenced by CagA-positive H. pylori strains, so that maximum levels of IL-18 were detected in DU patients with the CagA(+) phenotype, regardless of the presence of the anti-VacA antibody. Regarding IL-18 promoter polymorphisms, the AA genotype and A allele at position - 607C/A were found to be significantly lower in DU patients than in AS carriers and H. pylori-negative subjects (p = 0.032 and 0.043, respectively). CONCLUSIONS: The IL-18 - 607C variant was associated with higher levels of serum IL-18 and an increased risk of DU. Moreover, our findings indicated that serum concentrations of IL-18 were influenced by CagA factor, irrespective of the VacA status, suggesting that high levels of IL-18 in CagA-positive subjects predisposes to susceptibility to DU.

Evaluation of UDP-glucuronosyltransferase 2B17 (UGT2B17) and dihydrofolate reductase (DHFR) genes deletion and the expression level of NGX6 mRNA in breast cancer.

The present study was aimed to investigate the possible association between 19-base pair (bp) deletion polymorphism of the DHFR gene (rs70991108), null genotype of UDP-glucuronosyltransferase 2B17 (UGT2B17) as well as the expression level of nasopharyngeal carcinoma-associated gene 6 (NGX6) with the risk of breast cancer. This case-control study was done on 236 patients with breast cancer and 203 cancer free women. Detection of 19-bp del of DHFR was done using bi-directional PCR allele-specific amplification and UGT2B17 genotyping was performed using multiplex PCR assay. NGX6 mRNA expression level was determined by quantitative reverse transcriptase PCR in 62 breast cancerous and 62 adjacent non-cancerous tissues. Our finding showed an association between null genotype of UGT2B17 and risk of breast cancer and the null genotype increased susceptibility to breast cancer (OR: 2.99; 95 % CI: 1.94-4.60; p < 0.0001). However, no statistically significant difference was found between breast cancer patients and cancer free normal women regarding 19-bp ins/del of DHFR (χ(2) = 0.91, p = 0.63). Real-time PCR data showed that the relative expression level of NGX6 mRNA was significantly lower in cancerous than that in non-cancerous breast tissue specimens (0.936 ± 0.042 and 1.042 ± 0.039, respectively). However, NGX6 mRNA expression was not correlated with tumors grade (p > 0.05). In conclusion, the null genotype of UGT2B17 revealed to be a risk factor for breast cancer in a sample of Iranian population. Furthermore, down-regulation of NGX6 mRNA expression in breast carcinoma confirms the growing proof regarding the tumor suppressor role of NGX6.

Association of IRGM polymorphisms and susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran.

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. IRGM1 is an important protein in the innate immune response against intracellular pathogens by regulating autophagy. Polymorphisms in the IRGM genes are known to influence expression levels and may be associated with outcome of infections. This case-control study was done on 150 patients with PTB and 150 healthy subjects to determine whether the IRGM polymorphisms at positions -1208 A/G (rs4958842), -1161 C/T (rs4958843), and -947 C/T (rs4958846) were associated with PTB. The polymorphisms were determined using tetra-amplification refractory mutation system-PCR (T-ARMS-PCR). The results showed that the IRGM -1161 C/T and -947 C/T polymorphisms were associated with decreased susceptibility to PTB (OR = 0.06, 95% CI = 0.03-0.13, P < 0.001 and OR = 0.27; 95% CI = 0.013-0.55, P < 0.001, resp.). No significant difference was found among the groups regarding -1208 A/G polymorphism. In conclusion we found that the IRGM -1161 C/T and -947 C/T polymorphisms but not -1208 A/G polymorphism provide relative protection against PTB in a sample of Iranian population.

The relationship between IFN-γ and TNF-α gene polymorphisms and brucellosis: A meta-analysis.

BACKGROUND: Brucellosis is an infectious disease and one of the major public health problems worldwide. Several current studies have provided data that polymorphisms in the interferon-gamma gene (IFN-γ) and tumor necrosis factor-alpha gene (TNF-α) are related to brucellosis. OBJECTIVES: The aim of this study was to investigate the relationship between IFN-γ +874 A/T, IFN-γ UTR5644 A/T, TNF-α -308 G/A, and TNF-α -238 G/A single nucleotide polymorphisms (SNPs) and brucellosis risk by meta-analysis. MATERIAL AND METHODS: We performed a comprehensive search of the PubMed, MEDLINE, EMBASE, Web of Science, and Elsevier Science Direct databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of association between IFN-γ and TNF-α polymorphisms and brucellosis risk. RESULTS: A total of 17 studies including 1,904 cases and 2,233 controls fulfilled the inclusion criteria. Our pooled analysis demonstrated that the IFN-γ +874 AT vs AA genotype in a codominant model may confer an increased risk of brucellosis in the overall population (p = 0.001; OR = 0.51). Regarding TNF-α -308 G/A, our pooled analysis revealed that the AA vs GG + GA (recessive) genotype increased the risk of brucellosis (p = 0.02; OR = 2.00). CONCLUSIONS: In summary, our pooled analysis suggested that the IFN-γ +874 AT vs AA as well as the TNF-α -308 AA vs GG + GA genotypes demonstrated a trend for the association with a higher risk of brucellosis.

Interleukin-17 A and F gene polymorphisms affect the risk of tuberculosis: An updated meta-analysis.

BACKGROUND: Cytokines are fundamental elements in mediating and stimulating the immune response against tuberculosis (TB). Growing evidence indicated that polymorphisms in the interleukin-17 (IL-17) A and F genes are implicated in TB. OBJECTIVES: This meta-analysis was aimed to re-evaluate and update the relationship between IL-17A rs2275913 G/A and IL17F rs763780 T/C polymorphisms and TB risk. METHODS: Using inclusive searches of the PubMed, MEDLINE, EMBASE, Web of Science and Elsevier Science Direct, we identified outcome data from all articles estimating the association between IL-17 A and F polymorphisms and TB risk. RESULTS: A total of 15 studies comprising 7130 patients and 7540 controls were included. Our pooled analysis demonstrated that the IL-17A rs2275913 G/A SNP was not associated with the risk of TB in overall, or in Asians and Caucasians, but it conferred resistance to TB in Latin Americans using allele (OR=0.53), codominant (OR=0.53 and 0.38), dominant (OR=0.49) and recessive (OR=0.46) inheritance models. For IL-17F rs763780 T/C, the pooled evidence indicated that this variation was a risk factor for TB in allele (C vs T) and dominant (TC+CC vs TT) models in overall (OR of 1.35) and among Asians (OR=1.40), but not in Caucasians. CONCLUSION: In summary, our meta-analysis suggested that the IL-17A rs2275913 was a protective factor against TB, but -17F rs763780 T/C was a risk factor for TB.

Meta-Analysis of Risk Association Between Interleukin-17A and F Gene Polymorphisms and Inflammatory Diseases.

This meta-analysis examined the relationship between IL-17A (rs2275913) and IL17F (rs763780 T/C) gene polymorphisms and the risk of inflammatory diseases, including periodontitis, rheumatoid arthritis (RA), and inflammatory bowel disease. PubMed, MEDLINE, EMBASE, Web of Science, and Elsevier Science Direct were searched, and odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the strength of the association. A total of 25 studies comprising 7,474 cases and 10,628 controls were included. Significant associations were found between inflammatory diseases and IL-17A rs2275913 A versus G allele (OR = 1.197, P = 0.033) and the GA versus GG genotype in the codominant model (OR = 1.406, P = 0.036). Our findings suggested that individuals who carry the rs2275913 A allele or GA genotype have a 20% or 41%-increased risk of inflammatory diseases compared with subjects with the G allele or GG genotype, respectively. With respect to IL-17F rs763780, the C versus T allele (OR = 1.94; P = 0.040), the TC versus TT (OR = 1.39; P = 0.041), the CC versus TT (OR = 2.71; P = 0.003), as well as the TC + CC versus TT genotype (OR = 1.83; P = 0.032) were risk factors for RA. In summary, our pooled analysis indicated that the IL-17A (rs2275913) and IL17F (rs763780 T/C) increased the RA risk.

Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia-A case-control study from Iran.

We examined the possible relationship between three RAGE polymorphisms, -429C/T, -374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE -374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.

Hepatoprotective effects of curcumin in rats after bile duct ligation via downregulation of Rac1 and NOX1.

OBJECTIVES: New evidence has proven the hepatoprotective activity of curcumin; however, its underlying mechanisms remain to be elucidated. The aim of this study was to investigate the protective effect of curcumin on hepatic damage by measuring the antioxidant capacity and expression level of Rho-related C3 botulinum toxin substrate (Rac1), Rac1-Guanosine triphosphate (Rac1-GTP), and NADPH oxidase 1(NOX1) in biliary duct-ligated (BDL)-fibrotic rat model. METHODS: Wistar rats weighing 200 to 250 g were divided into four groups (n = 8 for each): sham group, sham+Cur group (received curcumin 100 mg/kg daily), BDL+Cur group, and BDL group. The mRNA and protein expression levels of Rac1, Rac1-GTP, and NOX1 were measured by real-time polymerase chain reaction and Western blotting, respectively. RESULTS: Curcumin treatment of BDL rats reduced liver injury, as verified by improvement of hepatic cell histologic alterations, and by reduction of hepatic enzymes. Moreover, the increase in the expression of Rac1, Rac1-GTP, and NOX1 observed in BDL rats was precluded and reversed back toward normalcy by curcumin treatment (P < 0.05). We also observed an escalation of protein thiol groups, increased enzyme activity of serum antioxidant markers (e.g., superoxide dismutase) and a decrease of carbonylation in curcumin-treated BDL rats compared with BDL rats (P < 0.05). CONCLUSIONS: Curcumin attenuated liver damage through the downregulation of Rac1, Rac1-GTP, and NOX1 as well as reduced oxidative stress in the serum and liver tissue of BDL rats.

The functional 4-bp insertion/deletion ATTG polymorphism in the promoter region of NF-KB1 reduces the risk of BC.

Nuclear factor kappaB (NF-kB) plays a key role in mammary gland development and breast cancer (BC) progression. A functional -94 insertion/deletion ATTG polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to affect NF-KB1 expression and confer susceptibility to different types of cancer. The current study aimed to assess the association of NFKB1 -94 insertion/deletion ATTG promoter polymorphism and BC risk in an Iranian population. A total of 439 subjects including on 236 BC patients and 203 healthy women were recruited. The NF-KB1 -94ins/del ATTG polymorphism was genotyped by Allele-Specific polymerase chain reaction (AS-PCR) method. Our results demonstrated that the NF-KB1 -94ins/del ATTG polymorphism was associated with a reduced risk of BC in Codominant (Ins/Ins vs. Del/Del: OR = 0.33, 95%CI = 0.17-0.64; P= 0.001), dominant (Ins/Ins vs. Ins/Del+Del/Del: OR = 0.64, 95%CI = 0.42-0.97; P= 0.027) and recessive (Ins/Del+Del/Del vs. Del/Del: OR = 0.40, 95%CI = 0.21-0.75; P= 0.002) tested inheritance models. Additionally, the Del allele of NF-KB1 -94ins/del ATTG variation with a higher prevalence in the control group compared to the BC patients (43.3% vs. 33.5%) was associated with a decreased risk of BC (OR = 0.66, 95%CI = 0.50-0.86, P= 0.003). In conclusion, our findings for the first time, suggest that the NF-KB1 -94ins/del Del allele and Del/Del genotype were associated with a reduced risk of BC which may contribute as protective factors against BC.

Relationship between CD14-159C/T gene polymorphism and acute brucellosis risk.

OBJECTIVE: To investigate the association between the cluster of differentiation 14 (CD14)-159C/T (rs2569190) gene polymorphism and susceptibility to acute brucellosis in an Iranian population. METHODS: The study included 153 Iranian patients with active brucellosis and 128 healthy individuals as the control group. Genotyping of the CD14 variant was performed using an amplification refractory mutation system-polymerase chain reaction method. RESULTS: The prevalence of CD14-159 TT and CT genotypes were associated with increased risk of brucellosis [odds ratio (OR) = 1.993, 95% confidence interval (95% CI) = 1.07-3.71, P = 0.03 for CT; OR = 3.869, 95% CI = 1.91-7.84, P = 0.01 for TT genotype. Additionally, the minor allele (T) was significantly more frequently present in brucellosis patients than in controls (61% vs. 45%, respectively), and was a risk factor for brucellosis (OR = 3.058, 95% CI = 1.507-6.315, P = 0.01). CONCLUSIONS: The findings provided suggestive evidence of association of the CD14-159C/T gene polymorphism with susceptibility to acute brucellosis in the Iranian population.

Promoter Methylation and mRNA Expression of Response Gene to Complement 32 in Breast Carcinoma.

Background. Response gene to complement 32 (RGC32), induced by activation of complements, has been characterized as a cell cycle regulator; however, its role in carcinogenesis is still controversial. In the present study we compared RGC32 promoter methylation patterns and mRNA expression in breast cancerous tissues and adjacent normal tissues. Materials and Methods. Sixty-three breast cancer tissues and 63 adjacent nonneoplastic tissues were included in our study. Design. Nested methylation-specific polymerase chain reaction (Nested-MSP) and quantitative PCR (qPCR) were used to determine RGC32 promoter methylation status and its mRNA expression levels, respectively. Results. RGC32 methylation pattern was not different between breast cancerous tissue and adjacent nonneoplastic tissue (OR = 2.30, 95% CI = 0.95-5.54). However, qPCR analysis displayed higher levels of RGC32 mRNA in breast cancerous tissues than in noncancerous tissues (1.073 versus 0.959; P = 0.001), irrespective of the promoter methylation status. The expression levels and promoter methylation of RGC32 were not correlated with any of patients' clinical characteristics (P > 0.05). Conclusion. Our findings confirmed upregulation of RGC32 in breast cancerous tumors, but it was not associated with promoter methylation patterns.

TNF-α -238, -308, -863 polymorphisms, and brucellosis infection.

BACKGROUND: Brucella abortus is an intracellular bacterium that affects humans and domestic animals. Tumor necrosis factor-alpha (TNF-α) has been shown as a key player in the induction of cell-mediated resistance against Brucella infection. We aimed to evaluate the possible influence of the TNF-α promoter polymorphisms (-308 G/A, -238 G/A, and -863 C/A) on the susceptibility of human brucellosis. METHODOLOGY: A total of 153 patients with active brucellosis and 128 healthy individuals were recruited. All subjects were genotyped for the polymorphisms in the TNF-α gene by Allele-Specific polymerase chain reaction analysis. RESULTS: Our results showed that the TNF-α -308 GG genotype was significantly more frequently present in controls than in brucellosis patients (91% vs. 75%), thus was a protective factor against developing brucellosis (OR=0.313, p=0.001). In contrast, the -308 GA genotype (OR=3.026, p=0.002) and minor allele (A) (OR=3.058, p=0.001) as well as AAG haplotype (OR=4.014, p=0.001) conferred an increased risk of brucellosis. However, the -238 G/A and -863 C/A polymorphisms were not associated with the risk of brucellosis at both allelic and genotypic levels (p>0.05). CONCLUSION: Our study revealed that the TNF-α -308 A allele or GA heterozygosity or AAG haplotype were associated with an increased risk of brucellosis in our population.

Peginterferon Alfa-2a/Ribavirin treatment efficacy in chronic hepatitis C patients is related to natural killer group 2D gene rs1049174 GC polymorphism.

Natural killer group 2D (NKG2D), as an activating receptor, plays pivotal role in viral infectious diseases. Several single nucleotide polymorphisms (SNPs) in the NKG2D gene have characterized that the rs1049174G/C SNP of NKG2D is in the spotlight of notice because of its role in activating of human T cells. This study aimed to investigate rs1049174G/C genetic polymorphism in Chronic Hepatitis C (CHC) patients. The study compromised 107 CHC patients with genotype 1a and 1b. All recruited patients were under treatment with Peginterferon Alfa-2a/Ribavirin according to standard protocol. After completing treatment, 67 patients showed sustained virologic response (SVR) and the rest of patients did not respond to the treatment and considered as non-responder (NR). Genotyping of NKG2D rs1049174G/C SNP was performed using PCR-RFLP method in SVR and NR patients. The NKG2D rs1049174 genotypes frequency for GG, GC and CC were 45, 41 and 14 % respectively. Genotypes distribution were significantly different between SVR and NR groups (p = 0.005). So that the patients with the homozygous GG genotype demonstrated a higher response to Peginterferon Alfa-2a/Ribavirin therapy against HCV infection (OR = 6.0, 95 %CI 1.71-21.08, p = 0.005). In conclusion, the rs1049174 GG genotype of NKG2D receptor is an effective factor in successfully treatment of CHC patients by Peginterferon Alfa-2a/Ribavirin.