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SHR Neuro Cancer Cardio Lipid Metab Microb

Mayerle, J; den Hoed, CM; Schurmann, C; Stolk, L; Homuth, G; Peters, MJ; Capelle, LG; Zimmermann, K; Rivadeneira, F; Gruska, S; Völzke, H; de Vries, AC; Völker, U; Teumer, A; van Meurs, JB; Steinmetz, I; Nauck, M; Ernst, F; Weiss, FU; Hofman, A; Zenker, M; Kroemer, HK; Prokisch, H; Uitterlinden, AG; Lerch, MM; Kuipers, EJ; Kuipers, E.
Identification of genetic loci associated with Helicobacter pylori serologic status.
JAMA. 2013; 309(18):1912-1920 Doi: 10.1001/jama.2013.4350 [OPEN ACCESS]
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Co-authors Med Uni Graz
Steinmetz Ivo

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Helicobacter pylori is a major cause of gastritis and gastroduodenal ulcer disease and can cause cancer. H. pylori prevalence is as high as 90% in some developing countries but 10% of a given population is never colonized, regardless of exposure. Genetic factors are hypothesized to confer H. pylori susceptibility. To identify genetic loci associated with H. pylori seroprevalence in 2 independent population-based cohorts and to determine their putative pathophysiological role by whole-blood RNA gene expression profiling. Two independent genome-wide association studies (GWASs) and a subsequent meta-analysis were conducted for anti-H. pylori IgG serology in the Study of Health in Pomerania (SHIP) (recruitment, 1997-2001 [n = 3830]) as well as the Rotterdam Study (RS-I) (recruitment, 1990-1993) and RS-II (recruitment, 2000-2001 [n = 7108]) populations. Whole-blood RNA gene expression profiles were analyzed in RS-III (recruitment, 2006-2008 [n = 762]) and SHIP-TREND (recruitment, 2008-2012 [n = 991]), and fecal H. pylori antigen in SHIP-TREND (n = 961). H. pylori seroprevalence. Of 10,938 participants, 6160 (56.3%) were seropositive for H. pylori. GWASs identified the toll-like receptor (TLR) locus (4p14; top-ranked single-nucleotide polymorphism (SNP), rs10004195; P = 1.4 × 10(-18); odds ratio, 0.70 [95% CI, 0.65 to 0.76]) and the FCGR2A locus (1q23.3; top-ranked SNP, rs368433; P = 2.1 × 10(-8); odds ratio, 0.73 [95% CI, 0.65 to 0.81]) as associated with H. pylori seroprevalence. Among the 3 TLR genes at 4p14, only TLR1 was differentially expressed per copy number of the minor rs10004195-A allele (β = -0.23 [95% CI, -0.34 to -0.11]; P = 2.1 × 10(-4)). Individuals with high fecal H. pylori antigen titers (optical density >1) also exhibited the highest 25% of TLR1 expression levels (P = .01 by χ2 test). Furthermore, TLR1 exhibited an Asn248Ser substitution in the extracellular domain strongly linked to the rs10004195 SNP. GWAS meta-analysis identified an association between TLR1 and H. pylori seroprevalence, a finding that requires replication in nonwhite populations. If confirmed, genetic variations in TLR1 may help explain some of the observed variation in individual risk for H. pylori infection.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Aged -
Aged, 80 and over -
Antigens, Bacterial -
Case-Control Studies -
Cohort Studies -
Female -
Genetic Loci -
Genetic Predisposition to Disease -
Genome-Wide Association Study -
Genome-Wide Association Study - epidemiology
Helicobacter Infections - epidemiology
Helicobacter Infections - genetics
Helicobacter pylori - isolation & purification
Humans -
Male -
Middle Aged -
Middle Aged - epidemiology
Polymorphism, Single Nucleotide -
Prevalence -
Seroepidemiologic Studies -
Toll-Like Receptor 1 - genetics
Young Adult -

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