Identification of genetic loci associated with Helicobacter pylori serologic status - PubMed (original) (raw)

Meta-Analysis

. 2013 May 8;309(18):1912-20.

doi: 10.1001/jama.2013.4350.

Caroline M den Hoed, Claudia Schurmann, Lisette Stolk, Georg Homuth, Marjolein J Peters, Lisette G Capelle, Kathrin Zimmermann, Fernando Rivadeneira, Sybille Gruska, Henry Völzke, Annemarie C de Vries, Uwe Völker, Alexander Teumer, Joyce B J van Meurs, Ivo Steinmetz, Matthias Nauck, Florian Ernst, Frank-Ulrich Weiss, Albert Hofman, Martin Zenker, Heyo K Kroemer, Holger Prokisch, Andre G Uitterlinden, Markus M Lerch, Ernst J Kuipers

Affiliations

Meta-Analysis

Identification of genetic loci associated with Helicobacter pylori serologic status

Julia Mayerle et al. JAMA. 2013.

Erratum in

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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).

Main outcomes and measures: H. pylori seroprevalence.

Results: 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.

Conclusions and relevance: 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.

PubMed Disclaimer

Comment in

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources