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| Home > Publications database > Toll-like receptor 1 locus re-examined in a genome-wide association study update on anti-Helicobacter pylori IgG titers. > print |
| 001 | 178524 | ||
| 005 | 20240229143549.0 | ||
| 024 | 7 | _ | |a 10.1053/j.gastro.2022.01.011 |2 doi |
| 024 | 7 | _ | |a pmid:35031300 |2 pmid |
| 024 | 7 | _ | |a 0016-5085 |2 ISSN |
| 024 | 7 | _ | |a 1528-0012 |2 ISSN |
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| 037 | _ | _ | |a DKFZ-2022-00121 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Lam, Suk Yee |b 0 |
| 245 | _ | _ | |a Toll-like receptor 1 locus re-examined in a genome-wide association study update on anti-Helicobacter pylori IgG titers. |
| 260 | _ | _ | |a Philadelphia, Pa. [u.a.] |c 2022 |b Saunders |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1651150741_30566 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a 2022 May;162(6):1705-1715 |
| 520 | _ | _ | |a A genome-wide significant association between anti-Helicobacter pylori (H. pylori) IgG titers and Toll-like receptor (TLR1/6/10) locus on 4p14 was demonstrated for individuals of European ancestry, but not uniformly replicated. We re-investigate this association in an updated genome-wide association study (GWAS) meta-analysis for low gastric cancer incidence populations, address potential causes of cohort heterogeneity and explore functional implications of genetic variation at the TLR1/6/10 locus.The dichotomous GWAS (25% individuals exhibiting highest anti-H. pylori IgG titers versus remaining 75%) included a discovery and replication sample of respectively n=15,685 and n=9,676, all of European ancestry. Longitudinal analysis of serological data was performed on H. pylori-eradicated subjects (n=132) and patients under surveillance for premalignant gastric lesions (n=107). TLR1/6/10 surface expression, TLR1 messenger RNA (mRNA) and cytokine levels were measured in leukocyte subsets of healthy subjects (n=26) genotyped for TLR1/6/10 variants.The association of the TLR1/6/10 locus with anti-H. pylori IgG titers (rs12233670; β=-0.267 SE±0.034; P=4.42x10-15) presented with high heterogeneity and failed replication. Anti-H. pylori IgG titers declined within 2-4 years following eradication treatment (P=0.004), and decreased over time in patients with premalignant gastric lesions (P<0.001). Variation at the TLR1/6/10 locus affected TLR1-mediated cytokine production and TLR1-surface expression on monocytes (P=0.016) and neutrophils (P=0.030), but not mRNA levels.The association between anti-H. pylori IgG titers and TLR1/6/10 locus was not replicated across cohorts, possibly due to dependency of anti-H. pylori IgG titers on therapy, clearance and antibody decay. H. pylori-mediated immune cell activation is partly mediated via TLR1 signaling, which in turn is affected by genetic variation. |
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| 700 | 1 | _ | |a Mommersteeg, Michiel C |b 1 |
| 700 | 1 | _ | |a Yu, Bingting |b 2 |
| 700 | 1 | _ | |a Broer, Linda |b 3 |
| 700 | 1 | _ | |a Spaander, Manon C W |b 4 |
| 700 | 1 | _ | |a Frost, Fabian |b 5 |
| 700 | 1 | _ | |a Weiss, Stefan |b 6 |
| 700 | 1 | _ | |a Völzke, Henry |b 7 |
| 700 | 1 | _ | |a Lerch, Markus M |b 8 |
| 700 | 1 | _ | |a Schöttker, Ben |0 P:(DE-He78)c67a12496b8aac150c0eef888d808d46 |b 9 |u dkfz |
| 700 | 1 | _ | |a Zhang, Yan |0 P:(DE-He78)d19149dd97b17ce55e70abd2f9e64d3d |b 10 |
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| 700 | 1 | _ | |a Levy, Daniel |b 13 |
| 700 | 1 | _ | |a Hwang, Shih-Jen |b 14 |
| 700 | 1 | _ | |a Wood, Alexis C |b 15 |
| 700 | 1 | _ | |a Rich, Stephen S |b 16 |
| 700 | 1 | _ | |a Rotter, Jerome I |b 17 |
| 700 | 1 | _ | |a Taylor, Kent D |b 18 |
| 700 | 1 | _ | |a Tracy, Russell P |b 19 |
| 700 | 1 | _ | |a Kabagambe, Edmond K |b 20 |
| 700 | 1 | _ | |a Leja, Marcis |b 21 |
| 700 | 1 | _ | |a Klovins, Janis |b 22 |
| 700 | 1 | _ | |a Peculis, Raitis |b 23 |
| 700 | 1 | _ | |a Rudzite, Dace |b 24 |
| 700 | 1 | _ | |a Nikitina-Zake, Liene |b 25 |
| 700 | 1 | _ | |a Skenders, Girts |b 26 |
| 700 | 1 | _ | |a Rovite, Vita |b 27 |
| 700 | 1 | _ | |a Uitterlinden, André |b 28 |
| 700 | 1 | _ | |a Kuipers, Ernst J |b 29 |
| 700 | 1 | _ | |a Fuhler, Gwenny M |b 30 |
| 700 | 1 | _ | |a Homuth, Georg |b 31 |
| 700 | 1 | _ | |a Peppelenbosch, Maikel P |b 32 |
| 773 | _ | _ | |a 10.1053/j.gastro.2022.01.011 |g p. S0016508522000191 |0 PERI:(DE-600)1478699-0 |n 6 |p 1705-1715 |t Gastroenterology |v 162 |y 2022 |x 0016-5085 |
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