Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population

Xh, Wang; Hp, Shi; Fj, Li

doi:10.4238/gmr.15037641

Cited by 3 publications

(6 citation statements)

References 18 publications

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“…The prevalence of TLR-9 genotypes for C-1237T, C-1486T, and C+2848T polymorphisms in healthy controls was comparable with earlier reports in Chinese population. [8][9][10][11][12] The prevalence of homozygous mutant (TT) for TLR-9 C-1237T polymorphism was significantly higher when compared to other genotypes, which is in line with earlier studies. 10,11 The high prevalence of heterozygotes or homozygous mutant in various populations has been attributed to the local selection pressure of several infectious diseases.…”

Section: Discussionsupporting

confidence: 90%

“…In addition, the prevalence of TLR-9 (C-1237T, C-1486T, and C+2848T) polymorphisms in healthy stomach was also not significantly different when compared to healthy controls of earlier published reports. 8,10,11 Interestingly, TLR-9 (C+2848T and C-1486T) mutants were more frequent in gastroduodenal ulcer patients compared to subjects with healthy stomach and healthy controls. These observations collectively suggest that TLR-9 polymorphisms possibly predispose subjects to development of gastroduodenal ulcer and related clinical complications.…”

Section: Discussionmentioning

confidence: 94%

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Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

Mai

Zhu

2018

Eur J Inflamm

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Helicobacter pylori infections have been one of the major factors associated with gastroduodenal ulcer. Toll-like receptors (TLRs) of human recognize mycobacterium-induced immune response and protect subjects from disease pathogenesis. Variants in TLR genes are believed to influence immune responses to H. pylori and clinical severity. TLR-9 polymorphisms have been associated with susceptibility to gastroduodenal ulcer in different populations. In this study, we investigate the role of common TLR-9 variants in susceptibility/resistance to the development of gastroduodenal ulcer in a Chinese cohort. The present hospital-based case-control study enrolled 580 patients with abdominal discomfort, and based on endoscopic investigation, the patients were categorized into (1) gastric ulcer (n = 154), (2) duodenal ulcer (n = 70), (3) gastric and duodenal ulcers (n = 25), (4) gastritis (n = 195), and (5) healthy stomach (n = 136). A total of 520 healthy controls from similar geographical areas were enrolled as controls. TLR-9 (C-1237T, C-1486T, and G+2848A) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in both healthy controls and patients were quantified by enzyme-linked immunosorbent assay (ELISA). Furthermore, messenger RNA (mRNA) expressions of TNFα, IL-6, and IL-1β in biopsy tissues were quantified by real-time polymerase chain reaction (RT-PCR). The prevalence of TLR-9+2848 heterozygotes (CT) was significantly higher in gastroduodenal ulcer patients compared to healthy controls. Sub-categorization of patients revealed higher prevalence of heterozygotes of TLR-9 C+2848T and C-1486T polymorphisms in patients with gastric ulcer (GU), duodenal ulcer (DU), and those with both gastric and duodenal ulcers (GDU) when compared to controls. Patients displayed higher plasma cytokine levels than healthy controls. TLR-9 polymorphisms (C+2848T and C-1486T) correlated with altered cytokine expression in biopsy tissues and their plasma levels. In conclusion, TLR-9 (C+2848T and C-1486T) polymorphisms are associated with gastroduodenal ulcer and correlated with altered cytokine levels.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 94%

Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

Mai

Zhu

2018

Eur J Inflamm

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“…Figure 1 shows the flow chart of meta-analysis search course. Based on the search strategy, four studies reporting seven groups of patients – three comprising both meningococcal (MM) and pneumococcal (PM) cases [9, 16, 17], and one reporting BM cases as a whole were identified [15] (Table 1). All but Wang's study used population-based controls.…”

Section: Resultsmentioning

confidence: 99%

“…TLR9 gene polymorphisms have also been associated with multiple diseases such as pulmonary tuberculosis, duodenal ulcers and altered cytokines in gastric mucosa, systemic lupus erythematosus and chronic obstructive pulmonary disease [10][11][12][13][14]. Of these polymorphisms, the rs352140 variant has been the one most investigated, and some have suggested that it is significantly associated with susceptibility to BM [15], but this has not been supported by other studies [9,16,17]. We therefore set out in this study to establish through a meta-analysis of published data whether TLR9 rs352140 polymorphism confers an increased risk for BM.…”

Section: Introductionmentioning

confidence: 99%

TLR9 Rs352140 polymorphism contributes to a decreased risk of bacterial meningitis: evidence from a meta-analysis

Xue

Peng

et al. 2020

Epidemiol. Infect.

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Some studies have suggested that the Toll-like receptor 9 polymorphism (TLR9 rs352140) is closely related to the risk of bacterial meningitis (BM), but this is subject to controversy. This study set out to estimate whether the TLR9 rs352140 polymorphism confers an increased risk of BM. Relevant literature databases were searched including PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (CNKI) up to August 2020. Seven case-control studies from four publications were enrolled in the present meta-analysis. Odds ratios (OR) and confidence intervals (95% CI) were calculated to estimate associations between BM risk and the target polymorphism. Significant associations identified were allele contrast (A vs. G: OR 0.66, 95% CI 0.59–0.75, P = 0.000), homozygote comparison (AA vs. AG/GG: OR 0.62, 95% CI 0.49–0.78, P = 0.000), heterozygote comparison (A vs. G: OR 0.74, 95% CI 0.61–0.91, P = 0.005), recessive genetic model (AA vs. AG/GG: OR 0.78, 95% CI 0.65–0.93, P = 0.006) and dominant genetic model (AA vs. AG/GG: OR 0.70, 95% CI 0.57–0.85, P = 0.000). The findings indicate that, in contrast to some studies, the TLR9 rs352140 polymorphism is associated with a decreased risk for BM.

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“…Especially the rs352140 variant has been, however, associated with infections such as malaria and meningitis. [ 53 , 57 ] Specifically, the minor T allele has been associated with increased inflammation and thereby increased symptoms of these infectious diseases, possibly indicating a stronger immune reaction, as also noted in placental inflammation. [ 29 , 58 ] Whether or not such increased inflammatory response also protects from the development of breast cancer remains to be characterized.…”

Section: Discussionmentioning

confidence: 99%

Lower frequency of TLR9 variant associated with protection from breast cancer among African Americans

et al. 2017

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IntroductionToll-like receptor 9 (TLR9) is an innate immune system DNA-receptor that regulates tumor invasion and immunity in vitro. Low tumor TLR9 expression has been associated with poor survival in Caucasian patients with triple negative breast cancer (TNBC). African American (AA) patients with TNBC have worse prognosis than Caucasians but whether this is due to differences in tumor biology remains controversial. We studied the prognostic significance of tumor Toll like receptor-9 (TLR9) protein expression among African American (AA) triple negative breast cancer (TNBC) patients. Germline TLR9 variants in European Americans (EAs) and AAs were investigated, to determine their contribution to AA breast cancer risk.MethodsTLR9 expression was studied with immunohistochemistry in archival tumors. Exome Variant Server and The Cancer Genome Atlas were used to determine the genetic variation in the general EA and AA populations, and AA breast cancer cases. Minor allele frequencies (MAFs) were compared between EAs (n = 4300), AAs (n = 2203), and/or AA breast cancer cases (n = 131).ResultsThirty-two TLR9 variants had a statistically significant MAF difference between general EAs and AAs. Twenty-one of them affect a CpG site. Rs352140, a variant previously associated with protection from breast cancer, is more common in EAs than AAs (p = 2.20E-16). EAs had more synonymous alleles, while AAs had more rare coding alleles. Similar analyses comparing AA breast cancer cases with AA controls did not reveal any variant class differences; however, three previously unreported TLR9 variants were associated with late onset breast cancer. Although not statistically significant, rs352140 was observed less frequently in AA cases compared to controls. Tumor TLR9 protein expression was not associated with prognosis.ConclusionsTumor TLR9 expression is not associated with prognosis in AA TNBC. Significant differences were detected in TLR9 variant MAFs between EAs and AAs. They may affect TLR9 expression and function. Rs352140, which may protect from breast cancer, is 1.6 X more common among EAs. These findings call for a detailed analysis of the contribution of TLR9 to breast cancer pathophysiology and health disparities.

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Association between Toll-like receptor 9 gene polymorphisms and risk of bacterial meningitis in a Chinese population

Cited by 3 publications

References 18 publications

Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

Association of TLR-9 polymorphisms with the development of gastroduodenal ulcer: A hospital-based study in a Chinese cohort

TLR9 Rs352140 polymorphism contributes to a decreased risk of bacterial meningitis: evidence from a meta-analysis

Lower frequency of TLR9 variant associated with protection from breast cancer among African Americans

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