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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The 19-bp deletion polymorphism of dihydrofolate reductase (DHFR) and nonsyndromic cleft lip with or without cleft palate: evidence for a protective role.

OBJECTIVE: Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are among the most common congenital birth defects worldwide. Several lines of evidence point to the involvement of folate, as well as folate metabolizing enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR) enzyme participates in the metabolic cycle of folate and has a crucial role in DNA synthesis, a fundamental feature of gestation and development. A functional polymorphic 19-bp deletion within intron-1 of DHFR has been associated with the risk of common congenital malformations. The present study aimed to evaluate the possible association between DHFR 19-bp deletion polymorphism and susceptibility to NS-CL/P in an Iranian population. MATERIAL AND METHODS: The current study recruited 100 NS-CL/P patients and 100 healthy controls. DHFR 19-bp deletion was determined using an allele specific-PCR method. RESULTS: We observed the DHFR 19-bp homozygous deletion genotype (D/D) vs. homozygous wild genotype (WW) was more frequent in controls than in NS-CL/P patients (25% vs. 13%), being associated with a reduced risk of NS-CL/P in both codominant (OR=0.33, P=0.027) and recessive (OR=0.45, P=0.046) tested inheritance models. We also stratified the cleft patients and reanalyzed the data. The association trend for CL+CL/P group compared to the controls revealed that the DD genotype in both codominant (OR=0.30, P=0.032) and recessive models (OR=0.35, P=0.031) was associated with a reduced risk of CL+CL/P. CONCLUSIONS: Our results for the first time suggested the DHFR 19-bp D/D genotype may confer a reduced risk of NS-CL/P and might act as a protective factor against NS-CL/P in the Iranian subjects.

The 19-bp deletion polymorphism of dihydrofolate reductase (DHFR) and nonsyndromic cleft lip with or without cleft palate: evidence for a protective role

Objective Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are among the most common congenital birth defects worldwide. Several lines of evidence point to the involvement of folate, as well as folate metabolizing enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR) enzyme participates in the metabolic cycle of folate and has a crucial role in DNA synthesis, a fundamental feature of gestation and development. A functional polymorphic 19-bp deletion within intron-1 of DHFR has been associated with the risk of common congenital malformations. The present study aimed to evaluate the possible association between DHFR 19-bp deletion polymorphism and susceptibility to NS-CL/P in an Iranian population. Material and Methods The current study recruited 100 NS-CL/P patients and 100 healthy controls. DHFR 19-bp deletion was determined using an allele specific-PCR method. Results We observed the DHFR 19-bp homozygous deletion genotype (D/D) vs. homozygous wild genotype (WW) was more frequent in controls than in NS-CL/P patients (25% vs. 13%), being associated with a reduced risk of NS-CL/P in both codominant (OR=0.33, P=0.027) and recessive (OR=0.45, P=0.046) tested inheritance models. We also stratified the cleft patients and reanalyzed the data. The association trend for CL+CL/P group compared to the controls revealed that the DD genotype in both codominant (OR=0.30, P=0.032) and recessive models (OR=0.35, P=0.031) was associated with a reduced risk of CL+CL/P. Conclusions Our results for the first time suggested the DHFR 19-bp D/D genotype may confer a reduced risk of NS-CL/P and might act as a protective factor against NS-CL/P in the Iranian subjects. .

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.

Effect of TP53 16-bp and ß-TrCP 9-bp INS/DEL polymorphisms in relation to risk of breast cancer.

P53 as a tumor suppressor and an apoptosis modulator, is the regulator of the cell cycle and apoptosis, and contributes to mammary gland development and breast cancer (BC) progression. BTRC gene (Homo sapiens beta-transducing repeat containing E3 ubiquitin protein ligase) encoded protein, ß-TrCP, is a novel regulator of p53. The current study aimed to assess the possible effects of TP53 IVS3 16 bp (rs17878362) and ß-TrCP 9 bp (rs16405) INS/DEL polymorphisms on BC risk in an Iranian population. A total of 439 women including 236 BC patients and 203 healthy women were recruited. The TP53 and ß-TrCP INS/DEL polymorphisms were genotyped by allele-specific polymerase chain reaction method. Our data demonstrated that the TP53 16-bp INS/DEL variation was associated with an increased risk of BC in codominant (INS/INS vs. DEL/DEL: OR=1.82; 95% CI=1.02-3.23; P=0.042) and dominant (Del/INS+INS/INS vs. DEL/DEL: OR=1.48; 95% CI=1.03-2.21; P=0.044) models. Additionally, the variant allele (INS) of TP53 DEL/INS polymorphism with a relatively higher frequency in cases than in controls (35.6 vs. 27.8) was a risk factor for BC (OR=1.43; 95% CI=1.06-1.93; P=0.017). With respect to ß-TrCP INS/DEL polymorphism, our study failed to find any difference in allele and genotype distribution between BC patients and controls in codominant, dominant and recessive tested inheritance models (P>0.05). Furthermore, no significant association among the ß-TrCP and TP53 genotype distribution and clinical characteristics of BC patients were found (P>0.05). Our findings suggest that the TP53 16-bp INS/INS and DEL/INS+INS/INS genotypes as well as the INS allele could be genetic factors related to BC risk.

TGFß1 genetic variants are associated with an increased risk of acute brucellosis.

OBJECTIVE: Cytokines play a critical role in the regulation of the immune response against brucellosis infection, and mediate production of many pro- and anti-inflammatory signals. Transforming growth factor-beta 1 (TGFß1), a powerful suppressive cytokine, inhibits macrophage activation and modulates T-cell function, and plays crucial roles in regulation of microbial replication and host responses to brucella. METHODS: The association of three polymorphisms in the TGFß1 gene (-509 C/T [rs1800469], + 868 C/T [rs1800470], and + 913 G/C [rs1800471]) in promoter, codons 10 and 25, respectively, with brucellosis infection was evaluated. This case-control study was performed on a total of 281 Iranian subjects including 153 patients with active brucellosis and 128 age- and sex-matched healthy individuals as controls. Genotyping for the TGFß1 -509 C/T and + 868 C/T variants was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Also, the + 913 G/C polymorphism was genotyped using an allele-specific PCR. RESULTS: The results demonstrated that the TGFß1 + 868 C/T mutant homozygote genotype (TT vs CC), was a risk factor for developing brucellosis in the co-dominant and recessive models (odds ratio (OR) = 2.60, p = 0.023; OR = 2.602, p = 0.014, respectively). Additionally, the diplotype analyses revealed that TGFß1 codon 10 and 25 diplotype, TT/GG, was associated with an increased risk of brucellosis (OR = 2.49, p = 0.038). Other TGFß1 variants did not increase the risk of brucellosis infection. CONCLUSIONS: Our findings propose that TGFß1 + 868 TT genotype and TT/GG diplotype may confer increased risk of brucellosis in the examined population.

Association between NPHS1 and NPHS2 gene variants and nephrotic syndrome in children.

INTRODUCTION: Nephrin and podocin proteins, encoded by NPHS1 and NPHS2 genes, are essential for the integrity of the glomerular filter. The present study was aimed to investigate whether NPHS1 rs437168 and NPHS2 rs61747728 genetic variants are involved in the susceptibility to nephrotic syndrome (NS). MATERIALS AND METHODS: This case-control study was performed on 108 children with NS and 97 healthy children. Genomic DNA was extracted from whole blood using the salting-out method. Polymorphism of the NPHS1 rs437168 and NPHS2 rs61747728 were detected by amplification refractory mutation system- and tetra primers amplification refractory mutation system-polymerase chain reaction, respectively. RESULTS: The results showed that the NPHS1 rs437168 GA as well as GA+AA genotypes increased the risk of NS in comparison with GG genotype (odds ratio, 4.76, 95% confidence interval, 2.31 to 9.80; P < .001 and odds ratio, 4.57; 95% confidence interval, 2.31 to 9.04, ; P < .001, respectively). The A allele was associated with increased risk of NS (odds ratio, 3.53; 95% confidence interval, 1.94 to 6.42, ; P < .001) in comparison to the G allele. No association was observed between NPHS2 rs61747728 polymorphism and NS. CONCLUSIONS: Our findings indicate that NPHS1 rs437168, but not NPHS2 rs61747728 variant, is associated with NS.

Association between Interleukin-1 Receptor Antagonist (IL1RN) Variable Number of Tandem Repeats (VNTR) Polymorphism and Pulmonary Tuberculosis.

Macrophages and T-lymphocytes are involved in immune response to Mycobacterium tuberculosis. Macrophage produces interleukin (IL)-1 as an inflammatory mediator. IL-1 receptor antagonist (IL1-Ra) is a natural antagonist of IL-1 receptors. In this study we aimed to examine the possible association between the variable number of tandem repeats (VNTR) of the IL-1 receptor antagonist (IL1RN) gene and pulmonary tuberculosis (TB) in a sample of Iranian population. Our study is a case-control study and we examined the VNTR of the IL1RN gene in 265 PTB and 250 healthy subjects by PCR. Neither the overall chi-square comparison of PTB and control subjects nor the logistic regression analysis indicated any association between VNTR IL1RN polymorphism and PTB. Our data suggest that VNTR IL1RN polymorphism may not be associated with the risk of PTB in a sample of Iranian population. Larger studies with different ethnicities are needed to find out the impact of IL1RN VNTR polymorphism on risk of developing TB.

Association between the apelin rs2235306 gene polymorphism and metabolic syndrome.

AIM: The rs2235306 of apelin polymorphism has been shown to be associated with fasting plasma glucose levels and hypertension. The present study aimed to investigate the impact of the apelin rs2235306 gene polymorphism on the risk of metabolic syndrome (MeS) in a sample of the Iranian population. MATERIALS AND METHODS: This population-based cross-sectional study was performed on 151 subjects with MeS and 149 without MeS, as defined by ATPIII criteria. Apelin rs2235306 polymorphism detection was done using the tetra amplification refractory mutation system-polymerase chain reaction. Because the apelin gene is located on the X chromosome, statistical analyses were conducted in a sex-specific manner. RESULTS: Our findings proposed that the apelin rs2235306 polymorphism was not associated with MeS susceptibility in the codominant, dominant, and recessive inheritance models tested (OR = 0.93, 95% CI = 0.51-1.71 for TC vs. TT; OR = 2.39, 95% CI = 0.70-8.16 CC vs. TT; OR = 1.09, 95% CI = 0.62-1.93 for TC+CC vs. TT; and OR = 2.45, 95% CI = 0.73-8.21 for CC vs. TT+TC). We found that the apelin TC+CC genotypes were associated with lower HDL-cholesterol in women without MeS. CONCLUSION: Our findings indicated no association between the apelin rs2235306 polymorphism and MeS. However, the results suggest that healthy females carrying apelin TC+CC genotypes have lower HDL-cholesterol in comparison with those carrying TT, which remains to be confirmed.