Effect of CD14 promoter polymorphism and<i>H. pylori</i>infection and its clinical outcomes on circulating CD14

Karhukorpi, Jari; Yan, Yongdong; Niemelä, Seppo; Valtonen, Jarno; Koistinen, P.; Joensuu, Tapio; Saikku, Pekka; Karttunen, Riitta

doi:10.1046/j.1365-2249.2002.01837.x

Cited by 86 publications

(76 citation statements)

References 43 publications

(44 reference statements)

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“…It was reported in a previous study that elevated sCD14 levels were associated with H. pylori infection, especially in subjects with the CD14 CC genotype (29). In the present study, we did not observe any significant elevation of sCD14 in subjects with H. pylori versus those without H. pylori, or in subjects with the CD14 À260CT or TT genotype versus those with the CC genotype either in cases and controls, although a nonsignificantly higher mean value of sCD14 was observed in subjects with the CC genotype and H. pylori infection.…”

Section: Discussionmentioning

confidence: 83%

Role ofCD14Promoter Polymorphisms inHelicobacter pyloriInfection–Related Gastric Carcinoma

Zhao¹,

Sun²,

Zhang³

et al. 2007

Clinical Cancer Research

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Purpose: Genetic variation in CD14 may affect CD14 expression and susceptibility to Helicobacter pylori infection^related cancers. This study examined functional single nucleotide polymorphisms (SNP) in the CD14 promoter and their associations with risk of developing gastric carcinoma in relation to H. pylori infection. Experimental Design: Thirty individual DNAs were sequenced to identify variants, and the function of the variants was examined by reporter gene assays. Genotypes and haplotypes were analyzed in 470 patients and 470 controls, and odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Serologic H. pylori antibody and soluble CD14 (sCD14) levels were measured by ELISA. Results: Two SNPs (À651C>T and À260C>T) were identified, of which the À260CT and À260TT genotypes were associated with elevated risk of gastric carcinoma (OR, 1.77; 95% CI, 1.09-2.85 and OR, 1.95; 95% CI, 1.20-3.16, respectively). Haplotype analysis suggested a synergistic effect of the two SNPs (OR for the T À651 -T À260 haplotype, 3.39 versus OR for the C À651 -T À260 haplotype, 1.45; P = 0.02), which is consistent with reporter gene assays. A multiplicative joint effect between H. pylori infection and À260C>T polymorphism was observed (OR for the presence of both À260TTgenotype and H. pylori infection, 4.03; 95% CI, 1.80-9.04). Patients had significantly higher sCD14 than controls (1,866 F 2,535 ng/mL versus1,343 F 2,119 ng/mL; P < 0.001), and this difference was associated with the CD14 À260 polymorphism and H. pylori infection. Conclusions: Functional polymorphism in CD14 is associated with greater risk of H. pylorir elated gastric carcinoma, which might be mediated by elevated sCD14.

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Section: Discussionmentioning

confidence: 83%

Role ofCD14Promoter Polymorphisms inHelicobacter pyloriInfection–Related Gastric Carcinoma

Zhao¹,

Sun²,

Zhang³

et al. 2007

Clinical Cancer Research

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“…The distribution of CC genotype in Taiwan is significantly low as compared with those in Western countries. 9,15,16 The mean fluorescence intensity (MFI) of mCD14 on PBMC and plasma levels of sCD14 were measured in 84 healthy individuals (age 20-45 years; mean7s.d., 23.874.3 years; 44 females and 40 males). As shown in Figure 1, mCD14 in TT genotypes (mean: 1818) are significantly higher than those in CT (mean: 1517; P ¼ 0.044) and CC (mean: 1603; P ¼ 0.034) genotypes.…”

Section: Resultsmentioning

confidence: 99%

A CD14 promoter polymorphism is associated with CD14 expression and Chlamydia-stimulated TNFα production

Eng¹,

Wang²,

Chen³

et al. 2004

Genes Immun

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CD14, a pattern recognition receptor on monocyte and macrophage, plays a central role in innate immunity through recognition of bacterial lipopolysaccharide and initiation of inflammatory response. Recently, CD14/À260C4T promoter gene polymorphism has been found to be related to a risk of inflammatory diseases. Our results showed that the C allele frequency among Chinese in Taiwan was lower than those in Western countries. The membrane CD14 expression was significantly higher in TT as compared with CT and CC genotypes (P ¼ 0.034, 0.044, respectively). There was a higher level of soluble CD14 in TT and CT genotypes than in CC genotypes. In addition, TNFa production in whole blood was significantly higher in TT genotype than in CC genotype after stimulation by Chlamydiae. In conclusion, the single base pair polymorphism of CD14 promoter gene is associated with CD14 expression and Chlamydia-stimulated TNFa production, and may thus play some role in the chlamydia-induced inflammatory response.

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“…In addition, the severity of atrophic gastritis induced by longterm infection of Haemobartonella felis in CH3/He mice is significantly higher than that in LPS-nonresponder CH3/HeJ mice (47), which have an inactivating point mutation in Tlr4 (48). More recently, Karhukorpi et al (49) reported elevated serum levels of a soluble form of the CD14 molecule in Haemobartonella pyloriinfected individuals. Soluble CD14 binds to LPS and facilitates its signaling, and this study has shown that CD14 promoter polymorphism is associated with the disease outcome.…”

Section: Discussionmentioning

confidence: 99%

Essential Role of MD-2 in TLR4-Dependent Signaling during Helicobacter pylori-Associated Gastritis

Ishihara

Rumi

Kadowaki

et al. 2004

The Journal of Immunology

147

138

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TLR4, a member of pattern recognition receptors, is the main receptor of LPS. MD-2 physically associates with TLR4 on the cell surface and confers LPS responsiveness. Helicobacter pylori LPS is one of the major virulence factors for induction of gastritis. We demonstrated in this study the role of MD-2 in TLR4-dependent signaling in H. pylori-associated gastritis. Gastric biopsy samples collected from patients with and without H. pylori infection and four gastric cancer cell lines were used for this study. TLR-4 and MD-2 expression in biopsy specimens and the cell lines was examined by using RT-PCR. Localization of TLR-4 in histological sections was evaluated by immunohistochemistry. For in vitro functional assays, we established stable transfectants of AGS cells expressing TLR4 and MD-2. Cellular distribution of TLR4 was examined by flow cytometry. NF-κB activation and activation of IL-8 and MD-2 promoters were assessed by reporter gene assay. H. pylori infection up-regulated the TLR4 and MD-2 expression in gastric mucosa. TLR4 staining was observed predominantly in epithelial cells, located in both the cytoplasm and at the apical surface. MD-2 transfection in AGS cells markedly increased cell surface expression of TLR4 and augmented the activation of NF-κB and IL-8 promoter upon stimulation with H. pylori LPS. Live H. pylori also stimulated transcriptional activation of MD-2. This study revealed that MD-2 expression is elevated in gastric epithelial cells during H. pylori infection, suggesting that the TLR4/MD-2 system is a potent receptor complex involved in the response to H. pylori LPS in the stomach.

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Effect of CD14 promoter polymorphism andH. pyloriinfection and its clinical outcomes on circulating CD14

Cited by 86 publications

References 43 publications

Role ofCD14Promoter Polymorphisms inHelicobacter pyloriInfection–Related Gastric Carcinoma

Role ofCD14Promoter Polymorphisms inHelicobacter pyloriInfection–Related Gastric Carcinoma

A CD14 promoter polymorphism is associated with CD14 expression and Chlamydia-stimulated TNFα production

Essential Role of MD-2 in TLR4-Dependent Signaling during Helicobacter pylori-Associated Gastritis

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