Lack of association of Toll-like receptor 2 Arg753Gln with cutaneous leishmaniasis

The aim of the present study was to investigate the frequency of Arg753Gln and Arg677Trp polymorphisms of TLR2 in patients with cutaneous leishmaniasis (CL) compared to healthy controls. The polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system assay (ARMS-PCR). The results showed that the frequency of Arg753Gln genotype was 14.3% and 10.1% in CL patients and normal controls, respectively. No one in either group was homozygous for the mutation. There was no significant difference in the genotype frequency. In contrast to the results for Arg753Gln polymorphism, we did not detect any case with Arg677Trp polymorphism in either control or patient group. In conclusion the TLR2 mutations are found equally in CL patients and healthy subjects.     

Arg753Gln Polymorphism of the Human Toll-like Receptor-2 Gene in Children with Recurrent Febrile Infections

Polymorphisms in toll-like receptors (TLRs) have been reported to increase susceptibility for some diseases. TLR-2 gene polymorphisms in Turkish children with recurrent respiratory tract infections and without well-known humoral immunodeficiencies were examined. The study consisted of 52 children with recurrent infections (study group) and 91 healthy children with a maximum of two infections in a year (control group). Recurrent infection was defined as the presence of at least six febrile bacterial infection episodes in a year. Not only TLR-2 gene polymorphisms but also immunoglobulins (IgG, IgM, IgA), IgG subsets (G1, G2, G3), and specific antibody levels (anti-tetanus and anti-hemophilus influenza) were determined to exclude humoral immunodeficiencies. The Arg753Gln and Arg677Trp polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism. The Arg753Arg genotype was significantly decreased in the study group compared to the control (P < 0.05). Children with recurrent infections were also found to be more frequently Arg753Gln heterozygous (P < 0.05), and their Gln allele distribution was higher than that of the control subjects (23% vs. 4.9%; P < 0.001). In contrast to these results, we did not detect any case with Arg677Trp polymorphism in both groups. These results have indicated that there is a strong significant relationship between susceptibility to recurrent bacterial infections and Arg753Gln polymorphism of the TLR-2 gene.     

Relationship between the TLR2 and TLR4 gene polymorphisms with a predisposition to certain urogenital infections

The distribution of the TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms among residents of Poltavsky region was studied. The relationship between these polymorphisms and the presence of diseases caused by urogenital infections was also studied. The population control group was a random sample of residents of Poltavsky region (n = 299); the group of patients with urogenital diseases consisted of 156 individuals. PCR and subsequent restriction analysis were used to enable the genotyping of the following TLR polymorphisms in these groups: Arg753Gln, Asp299Gly, and TLR4 Thr399Ile. We found a statistically significant correlation between the presence of allele A of the TLR2 gene (p = 0.0018) and allele G of the TLR4 gene (p = 0.085) and the presence of urogenital diseases.     

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

BackgroundThe associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations.MethodsA systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality.ResultsThirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn’s disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models.ConclusionsThe meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted.     

Relationship of TLR2 and TLR4 gene polymorphism with a penchant for individual urogenital infections

We investigated the population prevalence of polymorphisms of Arg753Gln TLR2gene, and Asp299Gly, Thr399Ile TLR4 genes among people living in the Poltava region, as well as data communication polymorphisms with the presence of diseases caused by urogenital infections. The group of population control was a random sample of residents of the Poltava region (n = 299). The group of patients with urogenital diseases included 156 people. Genotyping of these groups TLR2 Arg753Gln polymorphism and the gene TLR4 Asp299Gly, Thr399Ile was performed using PCR and subsequent restriction analysis. Statistically significant association of allele A ofgene TLR2 (p = 0.0018) and allele G of gene TLR4 (p = 0.085) with the presence of urogenital diseases was confirmed.     

浙江地区汉族人群Toll样受体2基因Arg753Gln多态性和肺结核病相关性

应用聚合酶链反应-序列特异性引物方法(polymerase chain reaction with sequence specific primer,PCR-SSP),研究浙江地区汉族人群中Toll样受体2(Toll-like receptor2,TLR2)Arg753Gln(G2408A)单核苷酸多态性(single nucleotide polymorphism,SNP)分布及其与肺结核病的易感性的关系。分析了170名肺结核病患者和199名正常献血者TLR2基因Arg753Gln位点的基因型分布频率。结果表明,在170名肺结核病患者和199名正常献血者中,TLR2 Arg753Gln位点G/G基因型频率分别为58.23%和84.2%,G/A基因型频率分别为41.77%和15.8%,两种基因型在两组中相比较,差异显著,P<0.001。两组人群中均未发现有A/A基因型存在。TLR2基因Arg753Gln位点在浙江地区汉族人群中有其独特的分布规律,这个位点的多态性分布对肺结核病的发展有潜在的危险影响。     

TLR2 Arg677Trp polymorphism in leprosy: revisited

We investigated the Toll-like receptor 2 (TLR2) Arg677Trp polymorphism, associated with lepromatous leprosy in the Korean population and shown to abrogate TLR2-mediated signalling in response to mycobacterial ligands, in 286 Indian leprosy patients and 183 ethnically matched controls. The case-control comparison also involved investigation of possible variation(s) in the promoter region of the TLR2 gene. Genotyping results after direct PCR sequencing showed that the TLR2 Arg677Trp polymorphism associated with lepromatous leprosy in the Korean population is not a true polymorphism of the TLR2 gene and has resulted from the variation present in the 93% homologous duplicated region of TLR2 exon 3 present approximately 23 kb upstream.     

Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes

Toll-like, vitamin A and D receptors and other innate proteins participate in various immune functions. We determined whether innate gene-sequence variations are associated with rubella vaccine-induced cytokine immune responses. We genotyped 714 healthy children (11–19 years of age) after two doses of rubella-containing vaccine for 148 candidate SNP markers. Rubella virus-induced cytokines were measured by ELISA. Twenty-two significant associations (range of P values 0.002–0.048) were found between SNPs in the vitamin A receptor family (RARA, RARB, TOP2B and RARG), vitamin D receptor and downstream mediator of vitamin D signaling (RXRA) genes and rubella virus-specific (IFN-γ, IL-2, IL-10, TNF-α, and GM-CSF) cytokine immune responses. A TLR3 gene promoter region SNP (rs5743305, −8441A > T) was associated with rubella-specific GM-CSF secretion. Importantly, SNPs in the TRIM5 gene coding regions, rs3740996 (His43Tyr) and rs10838525 (Gln136Arg), were associated with an allele dose-related secretion of rubella virus-specific TNF-α and IL-2/GM-CSF, respectively, and have been previously shown to have functional consequences regarding the antiviral activity and susceptibility to HIV-1 infection. We identified associations between individual SNPs and haplotypes in, or involving, the RIG-I (DDX58) gene and rubella-specific TNF-α secretion. This is the first paper to present evidence that polymorphisms in the TLR, vitamin A, vitamin D receptor, and innate immunity genes can influence adaptive cytokine responses to rubella vaccination.     

A common IL-13 Arg130Gln single nucleotide polymorphism among Chinese atopy patients with allergic rhinitis

Allergic rhinitis is a major public health problem and has seen its prevalence increase during the past few decades. Interleukin 13 (IL-13) has been implicated in the pathogenesis and in the regulation of immunoglobulin E (IgE) production. Single nucleotide polymorphisms (SNPs) have been found in both the coding sequence and the promoter region of IL-13, and such SNPs have been associated with allergic asthma. We have investigated whether IL-13 SNPs are associated with allergic rhinitis. Among 188 Chinese adult patients with allergic rhinitis and 87 normal controls, no significant difference was found in either allele or haplotype frequency of the SNPs between the two groups. Within patients, there was a significant association of the IL-13 Arg130Gln SNP, but not of the IL-13 promoter –1112(C/T) SNP, with serum total IgE levels. Patients with a Gln/Gln genotype showed much higher serum total IgE than those with an Arg/Arg genotype. When tested for serum-specific IgE, patients allergic to Derp 1, but not those allergic to Artemisia pollen, showed a significant association with the IL-13 promoter SNP. Thus, our results suggest a possible involvement of IL-13 SNPs in the regulation of IgE production in response to allergens in this Chinese population.M. Wang and Z.-M. Xing should be considered as equal first authors     

Association between Polymorphisms in XRCC1 Gene and Treatment Outcomes of Patients with Advanced Gastric Cancer: A Systematic Review and Meta-Analysis

Background

Many reports have shown inconsistent results on the relationship between single nucleotide polymorphisms (SNPs) of X-ray repair cross complementing protein (XRCC1) gene and platinum-based chemotherapeutic efficacy. This meta-analysis aimed to summarize published data about the association between two SNPs of XRCC1 (Arg194Trp and Arg399Gln) and treatment outcomes of patients with advanced gastric cancer.

Methodology/Principal Findings

We retrieved the relevant articles from MEDLINE, Web of Knowledge, and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected according to specific inclusion and exclusion criteria. Study quality was assessed according to the guidelines outlined by Hayden, et al. and PRISMA guidelines. We estimated the odds ratio (OR) for response rate versus no response after platinum-based chemotherapy. Progression-free survival (PFS) and overall survival (OS) were evaluated by pooled Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs). We found that none of the XRCC1 Arg194Trp and Arg399Gln polymorphisms was significantly associated with tumor response. Stratified analysis by ethnicity or sensitivity analysis also showed that XRCC1 SNPs were not related with chemotherapy response. Patients with minor variant A allele were likely to have poorer 2-year survival rate than those with G/G genotype. However, in the group of 5-year follow up, there was no significant association between the A allele and OS yet.

Conclusions/Significance

There is no evidence to support the use of XRCC1 Arg194Trp and Arg399Gln polymorphisms as prognostic predictors of TR and PFS in gastric patients treated with platinum-based chemotherapy. The relationship between minor variant A allele and OS requires further verification.     

Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease

Lyme disease (LD) is caused by Borrelia burgdorferi and displays different stages, including localized, early disseminated, and persistent infection, all of which are associated with profound inflammatory reactions in the host. Induction of proinflammatory cytokines by B. burgdorferi is mainly mediated by outer surface proteins interacting with TLR-2/TLR-1 heterodimers. In this study, we show that TNF-alpha induction by Borrelia lysate was impaired in heterozygous TLR-2 knockout mice, while reactivity to lipoteichoic acid, another TLR-2 ligand signaling via TLR-2/TLR-6 heterodimers, was unaffected. Blood from individuals heterozygous for the TLR-2 polymorphism Arg753Gln was tested for cytokine release upon stimulation with Borrelia lysate, and induction of TNF-alpha and IFN-gamma was significantly lower as compared with individuals not exhibiting this variation. Overexpression of TLR-2 carrying the Arg753Gln polymorphism in HEK 293 cells led to a significantly stronger impairment of activation by TLR-2/TLR-1 ligands as compared with TLR-2/TLR-6 ligands. To study whether heterozygosity for the Arg753Gln variant of TLR-2 influenced susceptibility for LD, we analyzed 155 patients for this polymorphism. The Arg753Gln variant occurs at a significantly lower frequency in LD patients as compared with matched controls (5.8 vs 13.5%, odds ratio 0.393, 95% confidence interval 0.17-0.89, p = 0.033), with an even more pronounced difference when late stage disease was observed (2.3 vs 12.5%, odds ratio 0.163, 95% confidence interval 0.04-0.76, p = 0.018). These data suggest that Arg753Gln may protect from the development of late stage LD due to a reduced signaling via TLR-2/TLR-1.     

Toll-like receptor 2 and Toll-like receptor 4 polymorphisms and susceptibility to asthma and allergic rhinitis: a case-control analysis

The aim of the study was to investigate whether polymorphisms in genes encoding Toll-like receptors (TLR2 and TLR4) may modify relative risk for development of asthma or allergic rhinitis. The results showed that the genotype and allele frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not significantly different between asthmatic children or allergic rhinitis when compared to controls (p>0.05 for each) or even when compared further with IgE level. However, it was shown that the mutant allele of TLR2 or TLR4 polymorphisms were significantly associated with the moderate-severe group compared to the mild group in both atopic asthmatics and allergic rhinitis group (p>0.001 for each). In conclusion, our study demonstrates a lack of association of TLR2 and TLR4 polymorphisms with asthma and allergic rhinitis but suggests significant association between these genetic variants and the disease severity.     

Polymorphisms of toll-like receptor 2 and 4 genes in Chagas disease

The aim of this study was to test the possible implication of toll-like receptor 2 (TLR2) and TLR4 gene polymorphisms in determining the susceptibility to Chagas' disease. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 475 individuals from Colombia, 143 seropositive with chagasic cardiomyopathy, 132 seropositive asymptomatic and 200 seronegative. The TLR2 arginine to glutamine substitution at residue 753(Arg753Gln) polymorphism was absent in the groups analyzed. The TLR4 Asp299Gly and Thr399Ile polymorphisms are in linkage disequilibrium and we observed a very low frequency of these polymorphisms in our study population (2.6% and 1.8% respectively). The overall TLR2 and TLR4 alleles and genotype distribution in seronegative and seropositive were not significantly different. We compared the frequencies between asymptomatic patients and those with chagasic cardiomyopathy and we did not observe any significant differences in the distribution of alleles or genotypes. In summary, this study corroborates the low frequency of TLR2 and TLR4 polymorphisms observed in other populations and suggest that these do not play an important role in Chagas' disease. The validation of these findings in independent cohorts is needed to firmly establish a role for TLR2 and TLR4 variants in Chagas' disease.     

Toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms and periodontitis susceptibility: a meta-analysis

The aim of this study was to determine whether the toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms confers susceptibility to periodontitis in ethnically different populations. A literature search using PubMed and Embase provided the data to conduct a meta-analysis on the associations between the TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, MMP-1 ?1607 G1/G2 and MMP-9 ?1562 C/T polymorphisms and periodontitis. A total of 32 studies (14 on TLR polymorphisms and 18 on MMP polymorphisms) were considered in the meta-analysis. The meta-analysis showed no association between periodontitis and the TLR2 753Arg allele (Odds ratio [OR] = 0.962, 95 % confidence interval [CI] = 0.662–1.400, p = 0.841). Meta-analysis of the TLR4 Asp299Gly and Thr399Ile polymorphisms showed no association between periodontitis and the TLR4 299Asp allele in all study subjects (OR = 0.984, 95 % CI = 0.761–1.271, p = 0.900; OR = 1.030, 95 % CI = 0.748–1.418, p = 0.854). Meta-analysis showed an association between the MMP-1 ?1607 G2G2 genotype and periodontitis in Asians (OR = 3.778, 95 % CI = 1.210–11.80, p = 0.022). Meta-analysis containing only studies in Hardy–Weinberg equilibrium revealed no association between chronic periodontitis and the MMP-9 ?1562TT genotype (OR = 0.638, 95 % CI = 0.265–1.533, p = 0.315). This meta-analysis demonstrates a lack of association between the TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, MMP-9 ?1562 C/T polymorphisms and periodontitis, but shows an association between the MMP-1 ?1607 G2G2 genotype and periodontitis in Asians.     

IL2-330G polymorphic allele is associated with decreased risk of Helicobacter pylori infection in adulthood

We evaluated whether polymorphisms in genes coding molecules linked to the innate and adaptive immune response are associated with susceptibility to Helicobacter pylori infection. IL1B-511C → T, IL1B-31 T → C, IL1RN allele 2, IL2-330 T → G, TNFA-307 G → A, TLR2Arg677Trp, TLR2Arg753Gln, TLR4Asp299Gly, and TLR5^392STOP polymorphisms were determined in 541 blood donors. IL2-330 T → G allele carriers had a decreased H. pylori infection risk (OR = 0.63, 95% CI = 0.43–0.93) after adjustment for demographic and environmental factors. Hence, we investigated whether the polymorphism is functional by evaluating IL-2 serum concentration in 150 blood donors and 100 children. IL-2 pro-inflammatory and anti-inflammatory properties were indirectly investigated by determining serum IFN-γ and IL-10/TGF-β levels. The polymorphism was associated with increased mean IL-2 levels in H. pylori-positive adults (2.65 pg/mL vs. 7.78 pg/mL) and children (4.19 pg/mL vs. 8.03 pg/mL). Increased IL-2 was associated with pro-inflammatory activity in adults (IFN-γ = 18.61 pg/mL vs. 25.71 pg/mL), and with anti-inflammatory activity in children (IL-10 = 6.99 vs. 14.17 pg/mL, TGF-β = 45.88 vs. 93.44 pg/mL) (p < 10⁻³ for all). In conclusion, in the context of H. pylori infection, IL2-330 T → G polymorphism is functional and is associated with decreased risk of infection in adults.     

Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk

Polymorphisms in DNA repair genes may be associated with differences in DNA repair capacity, thereby influencing the individual susceptibility to smoking-related cancer. We investigated the association of 10 base-excision and nucleotide-excision repair gene polymorphisms (XRCC1 -77 T/C, Arg194Trp, Arg280His and Arg399Gln; APE1 Asp148Glu; OGG1 Ser326Cys; XPA -4 G/A; XPC PAT; XPD Asp312Asn and Lys751Gln) with lung cancer risk in Caucasians. Genotypes were determined by PCR-RFLP and PCR-single base extension assays in 110 lung cancer patients and 110 age- and sex-matched controls, and the results were analyzed using logistic regression adjusted for relevant covariates. A significant association between the APE1 Asp148Glu polymorphism and lung cancer risk was found, with adjusted odds ratios (OR) of 3.38 (p=0.001) for the Asp/Glu genotype and 2.39 (p=0.038) for the Glu/Glu genotype. Gene-smoking interaction analyses revealed a statistically significant interaction between cumulative cigarette smoking and the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms: these polymorphisms were significantly associated with lung cancer in nonsmokers and light smokers (<25 PY; OR=4.92, p=0.021 for XRCC1 399 Gln/Gln; OR=3.62, p=0.049 for XPD 751 Gln/Gln), but not in heavy smokers (> or =25 PY; OR=0.68, p=0.566 for XRCC1 399 Gln/Gln; OR=0.46, p=0.295 for XPD 751 Gln/Gln). Both the XRCC1 Arg194Trp and Arg280His as well as the OGG1 Ser326Cys heterozygous genotypes were associated with a significantly reduced risk for lung cancer (OR=0.32, p=0.024; OR=0.25, p=0.028; OR=0.51, p=0.033, respectively). No associations with lung cancer risk were found for the XRCC1 -77 T/C, the XPA -4 G/A and the XPC PAT polymorphisms. In conclusion, the APE1 Asp148Glu polymorphism is highly predictive for lung cancer, and cumulative cigarette smoking modifies the associations between the XRCC1 Arg399Gln and the XPD Lys751Gln polymorphisms and lung cancer risk.     

Polymorphisms of Dectin-1 and TLR2 Predispose to Invasive Fungal Disease in Patients with Acute Myeloid Leukemia

Background

Patients with acute myeloid leukemia (AML) who undergo induction chemotherapy are at high risk for invasive fungal disease (IFD). Dectin-1, a C-type lectin family member represents one of the most important pattern recognition receptors of the innate immune system and single nucleotide polymorphisms (SNPs) in the Dectin-1 gene have been associated with an increased risk of infectious complications. We sought to investigate the impact of three different Dectin-1 SNPs and one TLR2 SNP on developing IFD in 186 adult patients with newly diagnosed AML following anthracycline-based induction chemotherapy.

Patients and methods

Genotyping of Dectin-1 SNPs (rs16910526, rs3901533 and rs7309123) and TLR2 SNP (rs5743708) was performed by TaqMan method and pyrosequencing. IFD was defined according to the EORTC/MSG consensus guidelines. Multiple logistic regression analyses were applied to evaluate the association between the polymorphisms and the occurrence of pulmonary infections. Dectin-1 expression studies with SNP genotyped human monocytes were performed to elucidate susceptibility to IFD following chemotherapy.

Results

We could demonstrate that patients carrying the Dectin-1 SNP rs7309123 G/G (n = 47) or G/G and C/G (n = 133) genotype revealed a significant higher risk for developing both pneumonia in general (adjusted odds ratio (OR): 2.5; p = 0.014 and OR: 3.0, p = 0.004) and pulmonary IFD (OR: 2.6; p = 0.012 and OR: 2.4, p = 0.041, respectively). Patients carrying the TLR2 SNP rs5743708 (R753Q, GA/AA genotype, n = 12) also revealed a significantly higher susceptibility to pneumonia including IFD. Furthermore, Dectin-1 mRNA expression in human monocytes was lower following chemotherapy.

Conclusion

To our best knowledge, this study represents the first analysis demonstrating that harbouring polymorphisms of Dectin-1 (rs7309123) or TLR2 (rs5743708) represents an independent risk factor of developing IFD in patients with AML undergoing induction chemotherapy.     

Genetic variants associated with the progression of hepatocellular carcinoma in hepatitis C Egyptian patients

Background

Hepatocellular carcinoma (HCC) associated to infection with hepatitis C virus (HCV) has become the fastest-rising cause of cancer-related deaths. Genetic variations may play an important role in the development of HCC in HCV patients. Ghrelin exerts anti-inflammatory, antifibrotic and hepatoprotective effects on chronically injured hepatic tissues. Ghrelin gene shows several single nucleotide polymorphisms (SNPs) including − 604G/A, Arg51Gln, and Leu72Met. Hemochromatosis gene (HFE) mutations namely C282Y and H63D may cause hepatic iron overload, thus increasing the risk of HCC in HCV patients.

Aim

To investigate the association of progression of HCC with ghrelin and HFE gene polymorphisms in HCV Egyptian patients.

Methods

Seventy-nine chronic HCV patients (thirty-nine developed HCC and forty did not), and forty healthy control subjects were included in the study. The polymorphisms were evaluated by PCR/RFLP analysis, and related protein levels were measured by either ELISA or colorimetric assays.

Results

The three tested SNPs on ghrelin gene were detected in the studied groups, only one SNP (Arg51Gln) showed significantly higher GA, AA genotypes and A allele frequencies in hepatitis C patients who developed HCC than in hepatitis C patients without HCC and controls. Of the two mutations studied on HFE gene only H63D heterozygous allele was detected, and its frequency did not statistically differ among studied groups.

Conclusion

Our results suggest that A allele at position 346 of the ghrelin gene is associated with susceptibility to HCC in hepatitis C patients.     

A polymorphism in the toll-like receptor 2 is associated with IL-12 production from monocyte in lepromatous leprosy

Toll-like receptor 2 (TLR2) is critical in the immune response to mycobacterial infections, and the mutations in the TLR2 have been shown to confer the susceptibility to infection with mycobacteria. We previously reported the detection of TLR2 Arg677Trp mutation in lepromatous leprosy. Here, the events triggered by TLR2 in response to cell lysate of Mycobacterium leprae(MLL), the causative agent of leprosy, were investigated. Upon stimulation with MLL, monocytes produced TNF-alpha and Interleukin-12 (IL-12), which play a role in the innate immune response to infection. Anti-TLR2 mAb blocked greater than 50% of the MLL-induced production of IL-12. We also performed the functional study on TLR2 by measurement of IL-12 production in serum and monocytes from leprosy patients with TLR2 mutation (Arg677Trp). The monocytes obtained from patients with the TLR2 mutation, in comparison to the wild-type TLR2, is significantly less responsive to MLL. It was also confirmed that patients with TLR2 mutation showed significantly lower serum levels of IL-12, in comparing with TLR2 wild-type. Our results reveal that innate immune response of monocytes against M. lepraeis mediated by TLR2, and suggest that the mutation in the intracellular domain of TLR2 gene is associated with IL-12 production in lepromatous leprosy.     

Polymorphisms of the Toll-Like Receptor 2 of Goats (Capra hircus) may be Associated with Somatic Cell Count in Milk

Toll-like receptor 2 (TLR2) plays an important role in recognition by the innate immune system of Gram-positive bacteria. As Gram-positive bacteria cause mastitis, we examined variations in the region of the TLR2 gene that codes for the extracellular domain. Samples of forty goats from a single dairy herd were collected, half with low SCC (≤200,000 cells/mL), and half with higher SCC. Two synonymous single nucleotide polymorphisms (SNPs) were identified: 840G?>?A and 1083A?>?G. One nonsynonymous SNP 739G?>?A was identified. This coded for valine or isoleucine, which have similar physiochemical properties, and was not in a region coding for a known functional domain. Surprisingly, the least square mean SCC of the heterozygous goats (146,220) was significantly lower than the SCC of homozygous GG goats (537,700; p?=?0.004), although these two groups were similar in days in milk (p?=?0.984), and there was no significant difference by breed (p?=?0.941). Because factors other than mastitis can affect SCC and our sample sizes were limited, additional studies are needed to corroborate an association between TLR2 genotype and SCC or mastitis in goats.