Detection of Toxoplasma gondii B1 Gene and IgM in IgG Seropositive Pregnant Women.

BACKGROUND: The onset of acute toxoplasmosis in pregnant women may pose a risk to their growing fetuses. The timely diagnosis of infection in managing the disease and preventing its harmful consequences on the fetus is very important. Therefore, the study was conducted to identify acute toxoplasmosis in the pregnant women by detecting the specific IgM antibody and Toxoplasma gondii B1 gene. METHODS: A total of 653 serum samples of women who attended to Fatemieh Hospital of Hamadan University of Medical Sciences were tested for IgG antibodies against Toxoplasma gondii by enzyme-linked immunosorbent as-say (ELISA). The IgG positive specimens were further examined for IgM by ELISA and polymerase chain reaction (PCR) for B1 gene. In the second phase, change in IgG titers was evaluated on 47 IgG positive samples after two weeks. RESULTS: ELISA data showed that 167 out of 653 and 2 out of 167 samples were positive for IgG (25.6%) and IgM (1.2%), respectively. However, PCR detection showed that 36 cases (21.6%) were positive for the B1 gene. Seven out of 47 IgG positive samples showed an increase in the antibody titer and positive for the B1 gene. The most cases of IgG positives and the B1 gene samples were associated with the third trimester of pregnancy with 49.7% and 14%, respectively, and the most common abundance of the B1 gene was 14.4% in the age group of 26 - 35. The most commonly reported clinical symptoms in the B1 gene-positive women were nausea 15 (41.7%), cough 13 (36.1%), headache 12 (33.3%), and vomiting 11 (30.5%). CONCLUSIONS: Using PCR and the B1 gene in serum samples of pregnant women to detect acute toxoplasmosis is a more appropriate and accurate method than IgM antibody.

HLA class II susceptibility pattern for type 1 diabetes (T1D) in an Iranian population.

This study aimed to determine the HLA-DRB1/HLA-DQB1 susceptibility and protection pattern for type 1 diabetes (T1D) in a population from Hamadan, north-west of Iran. A total of 133 patients with T1D were tested for HLA-DRB1 and HLA-DQB1 alleles using PCR-SSP compared to 100 ethnic-matched healthy controls. Alleles and haplotypes frequencies were compared between both groups. The most susceptible alleles for disease were HLA-DRB1*03:01, DRB1*04:02, DQB1*02:01 and DQB1*03:02, and protective alleles were HLA-DRB1*07:01, *11:01, *13:01, *14:01 and DRB1*15 and HLA-DQB1*06:01, *06:02 and *06:03. Haplotype analysis revealed that patients with T1D had higher frequencies of DRB1*03:01-DQB1*02:01 (OR = 4.86, P < 10(-7) ) and DRB1*04:02-DQB1*03:02 (OR = 9.93, P < 10(-7) ) and lower frequencies of DRB1*07:01-DQB1*02:01 (P = 0.0005), DRB1*11:01-DQB1*03:01 (P = 0.001), DRB1*13:01-DQB1*06:03 (P = 0.002) and DRB1*15-DQB1*06:01 (P = 0.001) haplotypes compared to healthy controls. Heterozygote combination of both susceptible haplotypes (DR3/DR4) confers the highest risk for T1D (RR = 18.80, P = 4 × 10(-5) ). Additionally, patients with homozygote diplotype, DR3/DR3 and DR4/DR4, showed a similar risk with less extent to heterozygote combination (P = 0.0004 and P = 0.01, respectively). Our findings not only confirm earlier reports from Iranians but also are in line with Caucasians and partly with Asians and some African patients with T1D. Remarkable differences were the identification of DRB1*04:01-DQB1*03:02, DRB1*07:01-DQB1*03:03 and DRB1*16-DQB1*05:02 as neutral and DRB1*13:01-DQB1*06:03 as the most protective haplotypes in this study.

Influence of IL-1RN intron 2 variable number of tandem repeats (VNTR) polymorphism on bipolar disorder.

BACKGROUND/AIMS: Several lines of evidence point to the role of neurobiological mechanisms and genetic background in bipolar disorder (BD). The interleukin-1 receptor antagonist (IL-1Ra) is the principal regulator of IL-1α and IL-1ß bioactivities. This study aimed to investigate the potential role of the variable number of tandem repeats (VNTR) polymorphisms of the IL-1Ra gene (IL1RN) in conferring susceptibility to BD. METHODS: In total, 217 patients meeting DSM-IV-TR criteria for BD and 212 controls were recruited for the study. Genotyping of IL1RN was determined by polymerase chain reaction amplification of VNTR of 86 base pairs in intron 2 of IL1RN. RESULTS: The genotype distribution of IL1RN polymorphism was significantly different between BD patients and controls. The IL1RN*1/2 genotype was more prevalent in BD patients than in controls (44.2 vs. 30.2%, p = 0.003). Multiple logistic regression analysis demonstrated that IL1RN*1/2 heterozygotes had a significantly higher risk for BD (OR 1.83 and 95% CI 1.22-2.74, p = 0.003). Further stratification of the BD patients into IL1RN*2 allele carrier and noncarrier subgroups revealed a strong association between IL1RN*2 carriage and prolongation of the disease (p = 0.02). CONCLUSIONS: These findings suggest a positive association between VNTR polymorphism in IL1RN and BD. Additional studies, particularly with a prospective approach, are necessary to clarify the precise role of the VNTR polymorphism on the disease in different ethnic populations.

Cholesteryl ester transfer protein (CETP) -629C/A polymorphism and it's effects on the serum lipid levels in metabolic syndrome patients.

Metabolic syndrome is a relatively common disorder with significant morbidity worldwide. Cholesteryl ester transfer protein (CETP) plays a central role in the metabolism of lipoproteins. In this study the effect of -629C/A polymorphism on the concentration of CETP and plasma lipids pattern was elicited in metabolic syndrome patients and control subjects. For this, a sample of 200 patients diagnosed with metabolic syndrome disorder was studied in comparison with 200 healthy controls. This study was performed by using polymerase chain reaction and restriction fragment length polymorphisms. Genotype distribution and allelic frequencies were determined and compared in metabolic syndrome and healthy controls. To determine the relationship between -629C/A polymorphism and lipid levels, lipids and CETP concentration were measured in metabolic syndrome and normal subjects. The results showed a significant difference between two groups in terms of FBS, cholesterol, TG, HDL-C, LDL-C levels as well as BMI, waist circumference, systolic and diastolic blood pressure. The genotype frequencies for this polymorphism differed significantly between metabolic syndrome patients and controls (in control group: CC% 20.5, CA% 76, AA% 3.5 and in patient group: CC% 28.5, CA% 53.5, AA% 18) (p < 0.05) while there was no significant difference in the frequency of the alleles. In the two groups, the levels of the cholesteryl ester transfer protein in AA genotype were lower than other genotypes. In the control group, individuals with AA genotype had the highest levels of LDL-C and TC plasma concentration. Considering the results of this study, it can be concluded that the -629 AA genotype was associated with high cholesterol; high LDL-C and low CETP level, so that it can be related to metabolic syndrome.

E-selectin and L-selectin polymorphisms in patients with periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is a multifactorial disease in which environmental and genetic determinant factors contribute to individual subjects susceptibility. A DNA polymorphism in the regulating region of adhesion molecule genes is suggested to modulate the molecules physiological effects. The aim of this study was to investigate the genetic association between the E-selectin Ser128Arg and L-selectin Phe206Leu polymorphisms and periodontitis. MATERIAL AND METHODS: DNA was isolated from the whole blood of 88 patients with periodontitis and 139 healthy individuals. All samples were genotyped for the E-selectin Ser128Arg and L-selectin Phe206Leu polymorphisms using the polymerase chain reaction with sequence specific primers. RESULTS: Our findings revealed a significant difference in the Ser128Arg polymorphism of E-selectin, but not in the L-selectin polymorphism, between periodontal patients and controls. The 128Arg allele was present more frequently in patients than in healthy individuals (31.25% vs. 12.2%, p < 0.0001). In addition, there was an association between the presence of the 128Arg allele and periodontitis (odds ratio 2.9; 95% confidence interval: 1.75-4.4, p < 0.0001). No significant association was found between the polymorphisms tested and the subgroups of periodontal disease (i.e. chronic periodontitis and aggressive periodontitis). CONCLUSION: The findings of this study showed that the Ser128Arg polymorphism of E-selectin might contribute to the susceptibility of Iranian individuals to periodontitis.

Gene polymorphism in transforming growth factor-beta codon 10 is associated with susceptibility to Giardiasis.

Secretory immunoglobulin A (S-IgA) antibodies have a central role in anti-Giardial defence. It has been demonstrated that transforming growth factor-beta1 (TGF-beta1) stimulates B lymphocytes to produce and secrete S-IgA. We sought to determine the association between TGF-beta1 polymorphism (T+869C) with susceptibility to Giardiasis. The TGF-beta1 genotypes and levels of salivary (S-IgA) were analysed in individuals with Giardiasis (97 symptomatic and 57 asymptomatic) and controls (n = 92). Individuals with symptomatic Giardiasis had the lowest levels of S-IgA compared to individuals in asymptomatic Giardiasis and control groups (97%, 73% and 43%, <1 g L(-1), respectively, P = 0.002). The frequency of allele C and CC genotypes of TGF-beta1 polymorphism was significantly higher among symptomatic patients than asymptomatic and control groups. Logistic regression analysis demonstrated that the individuals homozygous for allele C of TGF-beta1 had a significantly higher risk for symptomatic Giardiasis with odds ratio of 2.76 (95% CI: 3.88, 1.71, P = 0.007). Among the participants with TT genotype per cent of individuals with S-IgA level of more than 1 g L(-1) was almost twice the percentage in CC genotype individuals (14% versus 7% respectively P = 0.01). Our data suggest that CC genotype of TGF-beta1 polymorphism at codon 10 is associated with occurrence of Giardiasis.

Interleukin-4 (C-590T) and interferon-gamma (G5644A) gene polymorphisms in patients with periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is a multifactorial disease and immunologic and genetic factors have an important role in its pathogenesis. Mutation in the promoter regions of the interleukin-4 and interferon-gamma genes has been reported to modify the protein expression. The objective of this study was to evaluate the possible role of interleukin-4 (C-590T) and interferon-gamma (G5644A) polymorphisms in the susceptibility to periodontitis. MATERIAL AND METHODS: In this case-control study, 53 patients (36 women and 17 men), comprising 27 patients with aggressive periodontitis and 26 patients with chronic periodontitis, and 56 healthy volunteers, were enrolled. DNA was isolated from all subjects, and the polymerase chain reaction-sequence specific primer method was used to study the interleukin-4 (C-590T) and interferon-gamma (G5644A) gene polymorphisms. RESULTS: Our results showed no significant difference in the allele and genotype frequencies of interleukin-4 (C-590T) and interferon-gamma (G5644A) gene polymorphisms between patients with periodontal disease and controls. CONCLUSION: The results suggest that the interleukin-4 (C-590T) and interferon-gamma (G5644A) gene polymorphisms may not be associated with the susceptibility of Iranian individuals to periodontitis.

Transforming growth factor-beta1 polymorphisms in patients with brucellosis: an association between codon 10 and 25 polymorphisms and brucellosis.

This study examined the association between transforming growth factor (TGF)-beta1 polymorphisms and brucellosis. The TGF-beta1 genotypes at codons 10 and 25 were determined by an amplification refractory mutation system-PCR among 425 brucellosis patients and 213 healthy volunteers. The frequencies of TGF-beta1 codons 10 C and 25 G were significantly higher among patients than among controls, as was that of TGF-beta1 codon 10 C/C. The high-producer haplotype (CG/TG) was more frequent among patients than among controls. The findings suggest that genetic polymorphism in codons 10 and 25 of the TGF-beta1 gene might contribute to the development of brucellosis.

Pre- and Posttransplant IgA Anti-Fab Antibodies to Predict Long-term Kidney Graft Survival.

OBJECTIVES: Immunologic factors are reliable markers for allograft monitoring, because of their seminal role in rejection process. One of these factors is the immunoglobulin (Ig)A anti-Fab of the IgG antibody. This study aimed to evaluate the predictive value of pre- and posttransplant levels of this marker for kidney allograft function and survival. METHODS: Sera samples of 59 living unrelated donor kidney recipients were collected before and after transplantation (days 7, 14, and 30) and investigated for IgA anti-Fab of IgG antibody levels using enzyme-linked immunosorbent assay in relation with allograft outcome. RESULTS: Among 59 patients, 15 cases (25%) including 10 with acute rejection and 5 with chronic rejection episodes showed graft failure during a mean of 5 years of follow-up. High posttransplant levels of IgA anti-Fab antibodies were observed more frequently in patients with stable graft function (SGF) compared with patients with graft failure (P = 2 × 10(-6)). None of patients with acute or chronic rejection episodes had high levels of IgA anti-Fab antibodies at day 30 posttransplant compared with the SGF group (P = 10(-6) and P = .01, respectively). In addition, high levels of IgA anti-Fab antibody correlated with lesser concentration of serum creatinine at 1 month posttransplantation (P = .01). Five-year graft survival was associated with high levels of pre- and posttransplant IgA anti-Fab antibodies (P = .02 and P = .003, respectively). CONCLUSIONS: Our findings indicate the protective effect of higher levels of IgA anti-Fab antibodies regarding to kidney allograft outcomes and long-term graft survival.

Evaluation of C-reactive protein, a sensitive marker of inflammation, as a risk factor for stable coronary artery disease.

OBJECTIVES: Multiple lines of investigations have converged to suggest a prominent role for inflammation in coronary artery disease (CAD). The association of CRP level with active CAD is well documented. The relation, however, between levels of CRP and the presence and extent of stable CAD has seldom been studied in the developing countries. We investigated the association between serum concentration of C-reactive protein (CRP) and angiographically documented coronary artery disease (CAD) in a population of 450 individuals. DESIGN AND METHODS: Ultrasensitive immunoassay was used to measure CRP levels in 284 patients with CAD and 166 control healthy subjects. The association of CRP levels with severity of disease as indicated by > or = 50% stenosis in one vessel (n = 79), two vessels (n = 74), or three vessels (n = 131) was also investigated. RESULTS: CRP levels were greater in the patients with CAD (2.14 (0.88--3.38) vs. 1.45 (0.70--2.55) mg/L, p < 0.0001) than in the respective control subjects. Multiple logistic regression analysis showed CRP as an independent discriminating risk factor for CAD (odds ratio, 3.46, p < 0.001). Significant correlation was identified between CRP levels and severity of CAD (p < 0.0001). Prediction models that incorporated CRP in addition to other established coronary risk factors were significantly better at predicting risk than the models based on the other risk factors alone. CRP level was also an independent predictor of CAD in a subpopulation with normal levels of low density lipoprotein cholesterol (LDL-C < or = 3.4 mmol/L, p < 0.009). CONCLUSIONS: Our findings suggest that CRP has a strong association with stable CAD, as such, the measurement of CRP may improve the coronary risk assessment in Iranian CAD patients.

Influence of cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms in periodontitis.

AIM: Persistent host inflammatory immune response against the pathogens results in the destruction of periodontal tissues. Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a particularly important molecule in down-regulating T-cell expansion and cytokine production. This study aimed to assess three functional SNPs within CTLA-4 gene, -1722 T/C, -318 C/T, and +49 A/G in patients with aggressive or chronic periodontitis. MATERIALS AND METHODS: A total of 197 patients with periodontitis (71 aggressive and 126 chronic periodontitis) and 218 healthy controls were recruited. All samples were genotyped for CTLA-4 gene polymorphisms by polymerase chain reaction-amplification refractory mutation system (PCR-ARMS). RESULTS: The allelic and genotype frequencies of only +49 A/G SNP were more prominence in patients with chronic periodontitis (CP) than that controls (0.0005 and 0.001, respectively). Multivariate logistic regression analysis was demonstrated that homozygosity in +49 G/G had profoundly increased susceptibility for CP, OR=3.7 (95% CI; 1.6-8.5, P=0.001). In addition, comparison of CTLA-4 SNPs between patients with CP and aggressive periodontitis (AgP) revealed that heterozygosity in -1722 T/C polymorphism of CTLA-4 gene had a significantly higher risk for CP compared with AgP with a calculated odds ratio of 2.18 (95% CI; 1.17-4.06, P=0.01). CONCLUSION: These results suggest that CTLA-4 gene variants might be associated to susceptibility to specific form of periodontitis and participate in the CP development.

Interferon-gamma low producer genotype +5644 over presented in patients with focal brucellosis.

Genetic polymorphisms that affect production levels of certain cytokines may determine the risk, severity or protection in some infectious diseases like brucellosis. IFN-gamma plays a key role in the defense mechanism against brucella infection. This study aimed to determine the influence of the polymorphism within the +5644 position of IFN-gamma gene on the susceptibility to brucellosis. We investigated the allelic and genotypes distribution of A5644G polymorphism in IFN-gamma gene in an Iranian population comprising 259 patients with brucellosis and 238 healthy controls. The single nucleotide polymorphism was determined using the polymerase chain reaction in association with sequence-specific primers (PCR-SSP) incorporating mismatches at the 3'-end. Allelic and genotype frequencies of G5644A polymorphism of IFN-gamma gene were not significantly differed between patients with brucellosis and controls (p > 0.05). Stratification of patients to focal and non focal diseases revealed a significant increased of 5644A allele in patients with focal brucellosis (79.31% vs. 61.94%, p = 0.0005). Moreover, multivariate logistic regression models showed patients harboring the INF-y G5644A genotype were significantly more likely to develop focal infectious complications (OR = 3.45, p = 0.0004, 95% CI = 1.26-7.94). The present study suggests that the variant genotypes of G6544A of IFN-gamma might be associated with focal form of brucellosis and play as a genetic risk factor in brucellosis.

CD 28 gene polymorphism and plasma concentration of soluble CD 28 in Iranian patients with visceral leishmaniasis.

In visceral leishmaniasis (VL), the development of protective immunity is associated with expansion of leishmania-specific T-cell responses. Because of the essential role of CD28 in the effectiveness of T-cell activation, this study was carried out to investigate the CD28 gene polymorphism and plasma levels of soluble (s) CD28 molecule in Iranian patients with VL. Plasma concentrations of CD28 in 88 patients with VL, 132 individual with subclinical leishmaniasis, and 100 seronegative healthy controls were measured by enzyme-linked immunosorbent assay. Genotyping of CD28 gene polymorphism was performed by polymerase chain reaction based allotyping method using allele-specific primers for C or T at intron 3 position +17 in three groups. The frequency of CC genotype was significantly higher in subclinical VL patients (42.4%) than active VL group (27.3%) and healthy controls (16%) (P<0.001). Also, the frequency of allele C among subclinical VL group (57.6%) was significantly higher than active VL (40.9%) and control groups (34%) (p=0.003). No significant differences were observed between the plasma levels of sCD28 in three groups. Our findings suggest that the CD28 gene may have significant role in the protection of active VL in the Iranian population.

Evaluation of salivary glucose, IgA and flow rate in diabetic patients: a case-control study.

OBJECTIVE: An association between diabetes mellitus and alterations in the oral cavity has been noted. In this study, we evaluated differences between salivary IgA, glucose and flow rate in diabetic patients compared with healthy controls. MATERIALS AND METHODS: Forty patients with type 1 diabetes, 40 patients with type 2 diabetes and 40 healthy controls were selected. Whole unstimulated saliva samples were collected by the standard method and the salivary flow rate was determined. Nephelometric and Pars method were used to measure salivary IgA and salivary glucose concentrations, respectively. Statistical analysis was performed by Chi-square and t test. RESULTS: There were no significant differences in salivary IgA and glucose concentrations between type 1 and type 2 diabetic patients and their matched control subjects (P>0.05). Salivary flow rate was significantly lower in diabetic patients (P<0.05). In addition, DMFT was higher in diabetic patients than the controls. CONCLUSION: Determination of salivary constituents may be useful in the description and management of oral findings in diabetic patients.

Th-1/Th-2 cytokine pattern in human amoebic colitis.

Amoebiasis, caused by Entamoeba histolytica, is still considered a major health problem in developing countries. Since the immune response during human amoebiasis has not been clearly defined, we chose to evaluate cytokine production in patients suffering from amoebic colitis. A case-control association study was carried out on 62 subjects, including 31 patients with amoebic colitis and 31 healthy controls (age, sex and geographic region-matched). Serum levels of IL-12, IFN-gamma, IL-13 and IL-5 were measured by solid-phase sandwich enzyme linked immunosorbant assay. Serum levels of IFN-gamma, IL-12, IL-13 and IL-5 were higher in the patients with amoebic colitis than in healthy controls, but were only statistically increased for IL-5 (p = 0.04) and IL-13 (p = 0.014). Stratification of patients according to gender revealed that IL-13 was significantly elevated in men as compared to levels measured in women (p = 0.04). These findings suggest that E. histolytica induce a mixed Th-1/Th-2 response with a polarization toward Th-2 during the early stage of amoebiasis, which may aide in developing a clinical illness.

Rapid detection of intercellular adhesion molecule 1 (G241R and K469E) polymorphisms by a novel PCR-SSP assay.

Intercellular adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein member of the immunoglobulin superfamily and is actively involved in immune and inflammatory responses. We introduce a novel polymerase chain reaction-sequence-specific primers (PCR-SSP) method for rapid and simultaneous genotyping of ICAM-1 G241R and K469E polymorphisms. In a total of 184 DNA samples that have been previously analyzed for these polymorphisms using polymerase chain reaction-restriction fragment length polymorphism technique, re-genotyping of all samples with this new assay showed accurate and reproducible results. As PCR-SSP-based genotyping protocols are more convenient and cost-effective to do, it could therefore offer a valuable tool for assessment of ICAM-1 polymorphisms to which more confirmatory studies are needed.

Association of interleukin-1 receptor antagonist gene polymorphism and susceptibility to human brucellosis.

The aim of this study was to determine the influence of the polymorphism within the intron 2 of the interleukin-1 receptor antagonist gene (IL-1Ra) on the susceptibility to or development of brucellosis. A total of 255 patients with brucellosis and 162 healthy volunteers were genotyped for polymorphisms in intron 2 of the IL-1Ra gene. The frequency of allele 2 of the IL-1Ra gene was significantly higher in patients with brucellosis compared with the controls (24.5% vs 18.5%, P = 0.03). Although the heterozygosity was more prevalent in patients than in control individuals, it did not have any statistical significance (P = 0.1). Alleles 3, 4, and 5 were absent in our study population. This work is the first that verifies a significant association between genetic polymorphism of IL-1Ra and susceptibility to brucellosis.

Polymorphism in the promoter region of the CD14 gene and susceptibility to Brucellosis.

A single-nucleotide polymorphism in the promoter region of the CD14 gene at position 159 has been implicated in susceptibility to infectious diseases. We sought to determine the association between CD14 C-159 T functional promoter polymorphism and brucellosis in Western Iranian population where the disease is endemic. The CD14 genotype was determined in 228 patients with brucellosis from a rural area and 129 healthy volunteers from the same area. The prevalence of genotype TT was significantly higher in the patients while the controls showed higher prevalence of genotype CC (34.5% vs 15.5%, 15.4% vs 25.6%, P = 0.009). Multiple logistic regression analysis after adjustment for gender demonstrated that the patients who were homozygous for allele T of promoter of CD14 gene had a significantly higher risk for developing brucellosis with odds ratio of 3.03 (95% CI, 5.2, 1.75 P = 0.0004). The existence of homozygous genotype of allele T of CD14 was an independent determinant for occurrence of arthritis among the patients with brucellosis (odds ratio of 3.92 (95% CI, 2.93, 5.88, P = 0.001).Our findings provide suggestive evidence of association of the CD14 gene polymorphism with susceptibility to development of brucellosis in Iranian populations.

TLR4 polymorphism in Iranian patients with brucellosis.

OBJECTIVE: Brucellosis is a zoonosis of both public health and economic significance in most developing countries. Polymorphisms in Toll-like receptor-4 (TLR4) have been reported to be associated with a blunted immune response to microbial pathogens. Information regarding any association between genetic variation of TLR4 and susceptibility to brucellosis is not available in the literatures. The main purpose of this research is to evaluate the role of polymorphic alleles of TLR4 gene in susceptibility to brucellosis. MATERIALS AND METHODS: In this case-control study, 198 patients with brucellosis and 111 healthy volunteers matched for sex, age and geographic area were evaluated by genotyping for polymorphism in TLR4 gene (Asp299Gly) using amplification refractory mutation system (ARMS)-PCR method. RESULTS: Allele 896G was more prevalent in patients with brucellosis compared to healthy controls (33.6% vs. 20.7%, P=0.000003). Also the frequency of G allele of TLR4 gene was significantly higher in male patients with brucellosis compared to the same sex in control group (36% vs. 21.7%, P=0.00005). Multiple logistic regression analysis demonstrated that male patients heterozygous at allele G gene had a significantly higher risk for brucellosis with an odds ratio of OR 2.89, 95% CI: 1.79-4.69, P<0.0001). CONCLUSION: This study is the first to show an association between genetic polymorphism in TLR4 gene and susceptibility to brucellosis.