Genetic variants of TLR4 and TLR9 are risk factors for chronic Helicobacter pylori infection in South Indian Tamils

Toll like receptors (TLRs) are a class of molecular pattern recognition receptors, elicits a strong inflammatory immune response against pathogens. Helicobacter pylori (H. pylori), a gram negative flagellate colonizes the human stomach, is responsible for the development of chronic gastritis and gastric carcinoma. The higher incidence of H. pylori infection and gastric cancer in South Indian Tamils demands a genetic study to unravel the influence of TLR4 and TLR9 polymorphisms associated with chronic H. pylori infection. In this study, 230 healthy individuals and 77 patients diagnosed with H. pylori infection were screened for TLR4 (rs1927914, rs4986790, rs4986791) and TLR9 (rs352140, rs34399053, rs150459369) polymorphisms by PCR-RFLP and ARMS-PCR. We observed that the individuals harboring heterozygous and homozygous polymorphic variants of TLR4 conferred a significant risk to develop chronic H. pylori infection and peptic ulcer disease [rs4986790 AG, p = 0.001, OR-2.7, 95%CI: 1.5–5.03; GG, p = 0.0006, OR-9.8, 95%CI: 2.4–39.4; rs4986791CT, p = 0.0001, OR-7.2, 95%CI: 3.7–7.2; TT, p = 0.0001, OR-7.9, 95%CI: 2.6–23.7]. Also, the heterozygous variant of TLR9 rs352140, favoured the persistence of the H. pylori infection [p = 0.037, OR-1.87, 95%CI: 1.07–3.29]. Thus our findings suggest that TLR4 rs4986790, rs4986791 and TLR9 rs352140 polymorphisms are potential genetic risk factors influencing the disease susceptibility and clinical manifestation of chronic H. pylori infection in Indian Tamils.     

The relationship between TLR4 rs4986790 and rs4986791 gene polymorphisms and Helicobacter pylori infection in children with gastritis

BackgroundTLR4 is involved in H. pylori lipopolysaccharide recognition and its SNPs might be related to increased risk of developing premalignant conditions and gastric cancer. The objectives of the study were to evaluate the associations between both TLR4 rs4986790 and rs4986791 gene polymorphisms and H. pylori infection in children with gastritis.MethodsWe performed a cross-sectional study on 150 children admitted in a Tertiary Centre from Romania, between March 2016 and July 2018 in order to evaluate them regarding demographic, endoscopic, histopathological and TLR4 gene polymorphisms.ResultsOur final sample consisted of 50 children with H.pylori associated gastritis (group 1-Ghp group) and 97 children with gastritis without H.pylori infection (group 2). Poor socioeconomic status was a significant risk factor for H.pylori infection. We found no significant differences regarding the clinical symptoms and laboratory parameters between the two groups. Concordant results were found between the histopathological exam and rapid urease test. Variant genotypes of TLR4rs4986790 and TLR4rs4986791 gene polymorphisms acted as protective factors against H. pylori infection, without statistical significance.ConclusionsThe variant genotype of the TLR4 gene polymorphisms might be protective factors for H.pylori infection, while socioeconomic status is an risk factor for H. pylori infection. Urease test is a usefull diagnostic tool for H. pylori infection.     

Association of Toll-Like Receptors 2, 4, 9 and 10 Genes Polymorphisms and Helicobacter pylori-Related Gastric Diseases in Saudi Patients

Purpose: Helicobacter pylori is one of the most prevalent human pathogens worldwide. However, the outcomes of H. pylori infection are markedly variable from asymptomatic mild lesion to malignant transformation. Many factors are suggested to influence these infection outcomes, including host immunity and genetic susceptibility. Toll-like receptors (TLRs) can recognise different microbial components and play an essential role in the mucosal immune response against H. pylori infection. Materials and Methods: The association between the common single nucleotide polymorphisms (SNPs) in the genes of TLR2, 4, 9 and 10 and H. pylori-related gastric diseases were investigated by molecular methods after the confirmation of H. pylori infection. The study included 210 patients in three groups; chronic gastritis (n = 90), peptic ulcer disease (PUD) (n = 75) and gastric carcinoma (n = 45). Results: The results showed a significant association between TLR4 SNPs (rs4986790 and rs4986791) and the presence of H. pylori infection, especially in chronic gastritis patient group. Furthermore, TLR9-rs352140 TT genotype was more prevalent among chronic gastritis patient group. TLR10-rs10004195 TT genotype was found to be less prevalent among H. pylori-related chronic gastritis and PUD and was suspected to have a protective effect. TLR2 SNPs (rs3804099 and rs3804100) showed no significant statistical difference between H. pylori-infected patients and the controls. Conclusion: TLR genes polymorphisms may play a role in H. pylori infection susceptibility and may influence its outcomes; however, the ethnic and other factors may modify this effect.     

Polymorphism of TLR5 rs5744174 is associated with disease progression in Chinese patients with chronic HBV infection

Toll‐like receptors (TLRs) play a crucial role in innate and adaptive immunity, protecting the host from viral pathogens. Studies have implicated that TLR5 is associated with various diseases such as autoimmune and inflammation related diseases. However, little is known about the relationship between TLR5 and hepatitis B virus (HBV) infection. We studied the effect of TLR5 gene polymorphisms on susceptibility to and disease progression of chronic hepatitis B (CHB) infection in Chinese. Blood samples were taken from 636 patients with CHB, HBV‐related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 273 controls. Polymorphisms of TLR5 (1775A>G rs2072493 and 1846T>C rs5744174) were analyzed by PCR‐based sequencing. No difference in genotypic and allelic frequencies of TLR5 rs2072493 and rs5744174 was observed between patients and controls. Significant difference was found in frequency of TLR5 rs5744174 TT genotype between men with CHB and LC (p = 0.035). Frequency of TT genotype of TLR5 rs5744174 in patients positive for HBeAg was increased from 53.2% in patients with CHB to 74.1% in those with HCC (p = 0.024). Our results indicate that in Chinese genetic variation of TLR5 may be not a determinant of susceptibility to HBV‐related diseases but may play a role in development of HBV‐related severe liver diseases.     

Association of Helicobacter pylori infection with Toll‐like receptor‐4 Thr399Ile polymorphism increased the risk of peptic ulcer development in North of Iran

Toll‐like receptor‐4 (TLR4) polymorphisms may influence host immune response against Helicobacter pylori (H. pylori). This study aimed to investigate whether TLR4 polymorphisms are associated with H. pylori susceptibility and risk of peptic ulcer development or not. The TLR4 + 3725 G/C polymorphism was studied using polymerase chain reaction with confronting two‐pair primers (PCR–CTPP). In addition, TLR4 Asp299Gly and Thr399Ile polymorphisms were evaluated by PCR‐restriction fragment length polymorphism (RFLP). There was no significant difference in TLR4 + 3725 G/C and Asp299Gly genotype frequencies between non‐peptic ulcer (NPUD) and peptic ulcer (PUD) individuals in the context of peptic ulcer development and susceptibility to infection with H. pylori. Nevertheless, a significant association with increased risk for PUD development was observed for polymorphism TLR4 Thr399Ile [odds ratio (OR) = 4.2; 95% confidence interval (CI) = 1.35–13.26; p = 0.01]. Correspondingly, TLR4 Thr399Ile polymorphism was associated with H. pylori susceptibility (OR = 0.27; 95% CI = 0.08–0.88; p = 0.04). In addition, TLR4 Thr399Ile polymorphism increased 4.2‐fold, the risk of peptic ulcer development in individuals infected by H. pylori carrying CT + TT genotype. Our results showed that TLR4 Thr399Ile polymorphism along with H. pylori infection may play critical roles in peptic ulcer development in North of Iran.     

Altered Th17 Cytokine Expression in Helicobacter pylori Patients with TLR4 (D299G) Polymorphism

Helicobacter pylori (H. pylori) is associated with gastric ulcer and gastric adenocarcinoma. Polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. However, the details and association with different polymorphism and clinical expression of infection remain unclear. A case-control study consisting of 58 patients with H. pylori infection and 44 H. pylori uninfection was conducted. Genomic DNA was extracted and genotypes of TLR4 Asp299Gly polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mucosal cytokines expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. The expression of IL-6, IL-17, IL-21, IL-23 and TGF-β1 was signi?cantly higher in patients with D299G polymorphism in TLR4. But the expression of IL-18 between patients with single-nucleotide polymorphisms (SNPs) in TLR4 and patients with the wild-type allele was not signi?cant. In H. pylori-infected patients with gastritis, SNPs in TLR4 may alter cytokine expression toward Th17 immune response in the gastric mucosa and may have increased risk for the development of peptic ulcer.     

Association between Toll-Like Receptor 3 (TLR3) rs3775290, TLR7 rs179008, TLR9 rs352140 and Chronic HCV

Background: Inconsistent results were reported on the association of TLRs polymorphisms with the risk of HCV infection and HCV-related diseases.

Objective: to assess the relation between TLR3 rs3775290, TLR7 rs17900 and TLR9 rs352140 SNPs and chronic HCV in the Egyptian cohort and to study their relation to interferon response.

Methods: TLR3 rs3775290, TLR7 rs179008 and TLR9 rs352140 gene polymorphisms were typed by RFLP for 100 patients with chronic HCV and 25 with HCC in addition to 100 healthy controls.

Results: A significant higher frequency has been found for the CT genotype of TLR3 rs3775290 in chronic HCV infection (p < 0.001) and CC genotype and the combined genotype CC-AT-GA ♀ in controls (p < 0.001). Non-significant associations have been found for studied SNPs and HCC and response to interferon and also the viral load or the degree of fibrosis, however, the higher HCV viral load and the higher grade of fibrosis were associated with treatment failure (p < 0.001).

Conclusion: The heterozygous CT genotype of TLR3 rs3775290 may be a susceptibility risk factor for chronic HCV infection and the homozygous CC and the combined CC-AT-GA ♀ genotypes may be protective. The HCV viral load and the grades of liver fibrosis could be considered a risk factor for interferon treatment failure. It seems that the studied SNPs have no role in HCC development or failure of treatment. However, the small sample size is a limiting factor of the present study when interpreting the negative associations and that the current used cohort does not permit such conclusion.

Abbreviations: cHCV=chronic Hepatitis C virus, HCC=hepatocellular carcinoma, TLR=Toll like Receptor, RFLP=Restriction Fragment Length Polymorphism, SNP=Single Nucleotide Polymorphism, IFN-α= interferon alpha     

Genetic polymorphisms in the Toll-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer

Background

Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.

Methods

A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR–RFLP and real-time PCR.

Results

Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 −260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20–10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41–0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms).

Conclusions

Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.     

Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils

Background

Psoriasis is a chronic inflammatory disease of the skin. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is involved in the pathogenesis of psoriasis. Being highly polymorphic, several SNPs of VEGF have been reported to be associated with increased risk of psoriasis.

HLA‐G 14‐bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor?

H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA‐G), a non‐classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA‐G 14‐bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA‐G and its genetic polymorphisms in bacterial infection. Sixty‐eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA‐G 14‐bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14‐bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection.     

Interaction analysis between BLK rs13277113 polymorphism and BANK1 rs3733197 polymorphism,MMEL1/TNFRSF14 rs3890745 polymorphism in determining susceptibility to rheumatoid arthritis

Two pairwise genetic interactions (B cell lymphocyte kinase (BLK) rs13277113,B cell scaffold protein with ankyrin repeats 1 (BANK1) rs3733197and BLK rs13277113 membrane metalloendopeptidase like 1 (MMEL1)/ tumor necrosis factor receptor superfamily member 14 (TNFRSF14) rs3890745) have been demonstrated in determining susceptibility to rheumatoid arthritis (RA) without replication, thus this study was performed to examine whether abovementioned genetic polymorphisms were associated with RA and further tests were performed to see whether aforementioned genetic interactions existed in RA among Chinese population. A total of 328 patients with RA and 449 healthy control subjects were included in the current study. The polymorphisms were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. The association of RA with each polymorphism was analyzed by multivariate logistic regression model. Interaction analysis was done by multiple methods. Significant difference in genotype distribution of BLK rs13277113 polymorphism between RA patients and healthy controls was found (p?=?1.01?×?10^?2). The major allele A of BLK rs13277113 polymorphism was significantly increased in RA patients compared with controls (OR?=?1.36, 95% CI?=?1.08–1.71, p?=?9.27?×?10^?3). Significant association of RA with the major allele A of BLK rs13277113 polymorphism under dominant model was also detected (OR?=?2.74, 95% CI?=?1.42–5.29, p?=?2.73?×?10^?3). However, we did not find significant association between neither BANK1 rs3733197 polymorphism nor MMEL1/TNFRSF14 rs3890745 polymorphism and RA. Non-significant evidence was found for neither additive nor multiplicative interaction for these two pairwise genetic polymorphisms (BLK rs13277113-BANK1 rs3733197; BLK rs13277113-MMEL1/TNFRSF14 rs3890745). Significant association of RA with G allele of BANK1 rs3733197 polymorphism was only found among individuals carrying A/A genotype of the BLK rs13277113 polymorphism (OR?=?1.49, 95% CI?=?1.01–2.18, p?=?.04). In summary, our results indicated that the BLK rs13277113 polymorphism was involved in the genetic background of RA in Chinese population and the association of BANK1 rs3733197 polymorphism with RA was dependent on the genotype of BLK rs13277113 polymorphism, highlighting B-cell response implicated in the pathogenesis of RA.     

Single nucleotide polymorphisms rs2120131, rs4935047, and rs7095891 in the MBL2 gene show no association with susceptibility to chronic hepatitis B in a Chinese Han population

Thus far, many studies have evaluated the correlation between MBL2 gene polymorphisms and hepatitis B infection. Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between MBL2 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. There was no significant correlation between rs2120131, rs4935047, and rs7095891 and chronic HBV infection. This suggested that the new SNPs within MBL2 were not associated with susceptibility to chronic hepatitis B in a Chinese Han population. J. Med. Virol. 85:602–607, 2013. © 2013 Wiley Periodicals, Inc.     

TLR9 gene polymorphism (rs187084, rs352140): association with acute rejection and estimated glomerular filtration rate in renal transplant recipients

The Toll‐like receptors (TLRs) are related to innate immunity. TLR9, a member of TLRs, is expressed in immune cell–rich tissues and mediates cellular response. We investigated the association between TLR9 polymorphisms and kidney allograft outcomes. To investigate whether TLR9 polymorphisms are associated with acute rejection after renal transplantation, two single nucleotide polymorphisms (SNPs) of TLR9 gene (rs187084 ‐1486; rs352140, G2848A) were selected and genotyped by direct sequencing in 342 renal transplant recipients. SNPStats, SNPAnalyzer, Helixtree and Haploview version 4.2 were used to analyse genetic data. Multiple logistic regression models (codominant, dominant, recessive and log‐additive) were used to evaluate odds ratios (ORs), 95% confidence intervals (CIs) and P values. Both SNPs, TLR9 rs187084 ‐1486 and rs352140 G2848A, of recipients were associated with the risk of acute rejection in renal transplantation. C allele of rs187084 ‐1486 and A allele of rs352140 G2848A were protective genotype for acute rejection (OR 0.6, 95% CI 0.40–0.92; P = 0.018, OR 0.64, 95% CI 0.42–0.98; P = 0.04, respectively). rs187084 ‐1486 CT and rs352140 G2848A GA genotype were associated with a lower eGFR after a year of renal transplantation. TLR9 polymorphisms, rs187084 and rs352140, of recipients were associated with the risk of acute rejection in renal transplantation. The patients with rs187084 ‐1486 CT and rs352140 G2848A GA genotype showed a lower eGFR after a year of renal transplantation.     

Do CCR5 (CCR5Δ32) and TLR3 (RS5743313) gene polymorphisms prevent chronic hepatitis B infection?

Hepatitis B virus (HBV) is still a significant health problem in human. HBV severity or sensitivity of patients may be based on the individual genetic factors significantly. The aim of this study is to investigate the association of CCR5 (CCR5Δ32), TLR3 (rs5743313) functional gene polymorphisms, interferon-gamma (IFN-ɣ) level in HBV infection, which are thought to play an important role in innate and acquired immunity in patients who have undergone HBV seroconversion and those who have chronic hepatitis B disease and receive treatment. One hundred patients who are became naturally immune against HBV infection (HBsAg negative, anti-HBc IgG, and anti-HBs IgG positive), and 100 patients with chronic hepatitis B infection (>6 months HBsAg positive) who are receiving oral antiviral therapy were compared for CCR5Δ32, TLR3 (rs5743313) genotypes and serum IFN-ɣ level. It was found that CCR5Δ32 polymorphism (Wt/Δ32 and Δ32/Δ32) was significantly higher in the chronic hepatitis B group (p = 0.048) but not for TLR3 gene polymorphism. However, serum IFN-ɣ level was significantly higher in the HBV seroconversion group (75 ± 89 ng/ml) than in the chronic hepatitis B group (4.35 ± 17.27 ng/ml) (p < 0.001). In conclusion, a higher CCR5Δ32 allele frequency in patients with chronic hepatitis B might be considered as a marker of progression to chronic hepatitis.     

Association of eNOS (G894T,rs1799983) and KCNJ11 (E23K,rs5219) gene polymorphism with coronary artery disease in North Indian population

BackgroundEndothelial nitric oxide synthase (eNOS) and potassium voltage-gated channel subfamily J member 11 (KCNJ11) could be the candidate genes for coronary artery disease (CAD). This study investigated the relationship of the eNOS (rs1799983) and KCNJ11 (rs5219) polymorphisms with the presence and severity of CAD in the North Indian population.MethodsThis study included 300 subjects, 150 CAD cases and 150 healthy controls. Single nucleotide polymorphism was evaluated by Polymerase chain reaction and Restriction fragment length polymorphism (PCR-RFLP). Analysis was performed by SPSS (version 21.0).ResultsWe observed that KK genotype of KCNJ11E23K (rs5219) polymorphism (P=0.0001) genotypes and K allele (P=0.0001) was found to be a positive risk factor and strongly associated with CAD. In the case of eNOSG894T (rs1799983) there was no association found with CAD.ConclusionThese results illustrate the probability of associations between SNPs and CAD although specific genetic polymorphisms affecting ion channel function and expression have still to be clarified by further investigations involving larger cohorts.     

Genetic polymorphisms of CCL1 rs2072069 G/A and TLR2 rs3804099 T/C in pulmonary or meningeal tuberculosis patients

CCL1, one of the members of the CC chemokine family, is an inflammatory mediator that stimulates the migration of human monocytes. CCL1 expression is induced by Mycobacterium tuberculosis and TLR ligands in macrophage. TLR2 plays critical role in host immune response against M. tuberculosis infection by regulating the macrophage activation and cytokine secretion. M. tuberculosis causes different clinical forms of tuberculosis (TB) disease. Single-nucleotide polymorphisms (SNPs) in the CCL1 gene and TLR2 gene may be associated with the development of different clinical forms of TB, depending on the different immune mechanisms. This study was to evaluate the possible association between CCL1 rs2072069 G/A or/and TLR2 rs3804099 T/C (T597C) polymorphisms and pulmonary tuberculosis (PTB) or/and tuberculous meningitis (TBM) in a sample of the Chinese adult population. A case-control study was designed to compare the allele frequency and genotype distribution between control (n=386) and TB (n=341) who had either PTB (n=230) or TBM (n=111). The genotype typing was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TLR2 variant genotype 597CC was associated with susceptibility to PTB rather than to TBM. In the male PTB subgroup, 597CC genotype was identified in a higher rate, compared with male control subgroup. This study demonstrates that T597C polymorphism of TLR2 is a risk factor for susceptibility to PTB rather than to TBM in a sample of Chinese adult population. Patient gender may affect the outcome of M. tuberculosis infection. TLR2 gene may influence the development of PTB and TBM by different immune mechanisms.     

Association between miRNA-146a rs2910164 (G/C) polymorphism with the susceptibility to chronic HBV infection and spontaneous viral clearance in an Iranian population

Hepatitis B virus (HBV) infection is one of the clinical dilemmas in chronic liver diseases. MicroRNAs (miRNAs) are small noncoding RNA molecules that play an important role in the pathogenesis of liver diseases and single nucleotide polymorphisms (SNPs) in miRNA genes affect the clinical course of HBV infection. Previous studies have shown that miRNA-146a rs2910164 polymorphism can be associated with the pathogenesis of liver diseases such as hepatocellular carcinoma. The present study investigated the association between miRNA-146a rs2910164 polymorphism and susceptibility to HBV infection in an Iranian population. The study comprised 266 patients with chronic HBV infection, 172 patients with spontaneous viral clearance (SVC) after acute HBV infection, and 266 healthy control adjusted for sex and age. The genotyping of the miRNA-146a rs2910164 polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our data revealed that GG genotype and G allele of miRNA-146a rs2910164 SNP is dominated (P < 0.001) in patients with chronic HBV infection (Odds ratio [OR] = 3.92; 95% confidence interval [CI] = 2.1-7.32). miRNA-146a rs2910164 polymorphism showed a statistically significant association (P < 0.001) between CC genotype and allele C with SVC (OR = 2.92; 95% CI = 1.56-546). Our findings suggest miRNA-146a SNP (C/G) in our population may be associated with the susceptibility to HBV infection and CC genotype is associated with SVC. Also, the GG genotype and G allele at miRNA-146a rs2910164 is associated with chronic HBV infection in our population.     

Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population — implications for association study design and clinical genetic testing services

We investigated the prevalence of genotypes/alleles of single nucleotide polymorphisms (SNP) and haplotypes defined by them in three genes in which variations are associated with venous thromboembolism in 80 Sinhalese, 80 Sri Lankan Tamils and 80 Moors in the Sri Lankan population and compared the SNP data with that of other populations in Southern India and haplotype data with that of HapMap populations. The genes and polymorphisms investigated were Methylenetetrahydrofolate reductase (MTHFR) — 677C>T (rs1801133), 1298A>C (rs1801131), 1317T>C, 1793G>A (rs2274976); Factor V (F5) — 1691G>A (rs6025) and 4070A>G (rs1800595); and prothrombin (F2) — 20210G>A (rs1799963). The polymorphisms were genotyped using PCR/RFLP methods. The prevalence of the variant alleles of each polymorphism in the Sinhalese, Tamils, and Moors was MTHFR 677T: Sinhalese — 13%, Tamils — 9%, Moors — 9%. 1317T>C: Sinhalese — 0%; Tamils — 0%; Moors — 0%. 1793A: Sinhalese — 19%, Tamils — 19%, Moors — 19%. F5 1691A: Sinhalese — 2%, Tamils — 3%, Moors — 2%. 4070G: Sinhalese — 6%, Tamils — 5%, Moors — 8%. F2 20210A: Sinhalese — 0%, Tamils — 0%, Moors — 0%. The frequencies observed were similar to data from other South Indian populations; the haplotype data showed haplotypes unique to the Sri Lankan population when compared to HapMap populations. rs9651118 was identified as a SNP that splits the haplotypes harbouring the functionally significant 677T allele in the MTHFR gene. This data would be useful in planning genetic association studies in the Sri Lankan population and in deciding on which genetic variants should be tested in a clinical genetic testing service.     

Association of genetic variants of membrane receptors related to recognition and induction of immune response with Helicobacter pylori infection in Ecuadorian individuals

Helicobacter pylori (Hp) has a worldwide distribution showing its higher prevalence of infection in developing countries. Toll‐like receptors (TLRs) and C‐type lectin receptors (CLRs) are proteins that recognize pathogen‐associated molecular patterns (PAMPs) and initiate an innate immune response by promoting growth and differentiation of specialized hematopoietic cells for host defense. Gastric infections led by Hp induce a Th‐1 cellular immune response, regulated mainly by the expression of IFN‐γ. In this retrospective case‐control study, we evaluated the TLR1 1805T/G, TLR2 2029C/T, TLR4 896A/G, CD209 ‐336A/G and IFNGR1 ‐56C/T polymorphisms and their relationship with susceptibility to Hp infection. TLR1 1805T/G showed statistical differences when the control (Hp‐) and infected (Hp+) groups (P = 0.041*) were compared; the TLR1 1805G allele had a protective effect towards infection (OR = 0.1; 95% CI = 0.01‐0.88, P = 0.033*). Similarly, the IFNGR1 ‐56C/T polymorphism showed statistical differences between Hp+ and Hp– (P = 0.018*), and the IFNGR1 ‐56TT genotype exhibited significant risk to Hp infection (OR = 2.9, 95% CI = 1.27‐6.54, P = 0.018*). In conclusion, the pro‐inflammatory TLR1 1805T and IFNGR1 ‐56T alleles are related with susceptibility to Hp infection in Ecuadorian individuals. The presence of these polymorphisms in individuals with chronic infection increases the risk of cellular damage and diminishes the cellular immune response efficiency towards colonizing agents.     

A 5′-flanking region polymorphism in toll-like receptor 4 is associated with gastric cancer in a Chinese population

Objective

Inflammation induced by H.pylori colonization in the stomach is related to the development of gastric cancer and the genetic variations of the genes involved in the immune responses modify the host response to the infection. The aim of this study was to evaluate whether polymorphisms in the toll-like receptor 4 (TLR4) gene, a key regulator of both innate and adaptive immunity, were related to the susceptibility to gastric cancer in a Chinese population.

Methods

Two variations in the 5′-flanking region of TLR4 (rs1927914 T > C and rs10759932 T > C) were genotyped by using the PCR-restriction fragment length polymorphism (RFLP) assay in a case-control study of 1,053 incident gastric cancer cases and 1,100 cancer-free controls in a Chinese population.

Results

Individuals carrying the C allele of rs10759932 had a significantly reduced risk of gastric cancer (adjusted OR = 0.81; 95%CI = 0.67-0.96), compared with the wild-type homozygote (TT), and the protective effect was not significantly different among subgroups stratified by age, sex, smoking, drinking and H.pylori infection status (P for heterogeneity > 0.05). No significant association was observed between rs1927914 and gastric cancer risk in this study population.

Conclusion

The T to C allele substitution of rs10759932 may play a protective role in gastric carcinogenesis in a Chinese population. Large studies with different ethnic populations are warranted to confirm these findings.