Association of 4p14 TLR locus with antibodies to Helicobacter pylori

abstract: ...A genome-wide association study among Europeans related polymorphisms of the TLR locus at 4p14 and the FCGR2A locus at 1q23.3 to Helicobacter pylori serologic status. We replicated associations of 4p14 but not 1q23.3 with anti- H. pylori antibodies in 1,402 Finnish males. Importantly, our analysis clarified that the phenotype affected by 4p14 is quantitative level of these antibodies rather than association with seropositivity per se . Additionally, we annotated variants at 4p14 as expression quantitative trait loci associated with TLR6/10 and FAM114A1. Our findings suggest that 4p14 polymorphisms are linked to host immune response to H. pylori infection but not to its acquisition.

...100953417 21482 Genes Immun Genes Immun. Genes and immunity 1466-4879 1476-5470 26312625 4670272 10.1038/gene.2015.33 NIHMS710283 Article Association of 4p14 TLR locus with antibodies to Helicobacter pylori Sung Hyuna 1 Camargo M Constanza 1 Yu Kai 1 Weinstein Stephanie J. 1 Morgan Douglas R. 2 Albanes Demetrius 1 Rabkin Charles S 1 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA 2 Division of Gastroenterology, Vanderbilt University, Nashville, TN, USA Correspondence to: Hyuna Sung, PhD, Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, 6E512, Bethesda, Maryland 20892, USA., Telephone: 240-276-7820, hyuna.sung@nih.gov 29 7 2015 27 8 2015 12 2015 18 5 2016 16 8 567 570 Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms A genome-wide association study among Europeans related polymorphisms of the TLR locus at 4p14 and the FCGR2A locus at 1q23.3 to Helicobacter pylori serologic status. We replicated associations of 4p14 but not 1q23.3 with anti- H. pylori antibodies in 1,402 Finnish males. Importantly, our analysis clarified that the phenotype affected by 4p14 is quantitative level of these antibodies rather than association with seropositivity per se . Additionally, we annotated variants at 4p14 as expression quantitative trait loci associated with TLR6/10 and FAM114A1. Our findings suggest that 4p14 polymorphisms are linked to host immune response to H. pylori infection but not to its acquisition. Introduction Chronic Helicobacter pylori infection is causally associated with gastritis, gastroduodenal ulcer disease, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. 1 A genome-wide association study (GWAS) of

... ENCODE cell lines, 17 SNPs were mapped to DNaseI hypersensitive regions and 42 SNPs altered binding motifs of at least one transcription factor. GTEx expression quantitative trait loci (eQTL) data on whole-blood samples identified multiple SNPs significantly correlated ( P <0.01) with mRNA transcript levels of TLR6/10 or FAM114A1 but not with TLR1 ( Supplementary Table 3 ). The low IgG allele (G) of rs6835514 was inversely associated with mRNA levels of TLR6 (beta=0.11; P =3.2e-3) and positively associated with FAM114A1 expression (beta=0.31; P =3.7e-5) ( Figure 2 ). Of particular interest, rs10034903, which was mapped to an active promoter of TLR10 as well as a transcription factor binding site, appeared to be a significant eQTL for both TLR10 and FAM114A1 ( Figure 2 ). Similar to rs6835514, the low IgG allele (G) of rs10034903 was associated with decreased mRNA expression of TLR10 (beta=0.13; P =6.5e-3) and increased mRNA expression of FAM114A1 (beta=0.27; P =8.0e-4). Although roles in

... regression was conducted for the 52 SNPs on log and quantile normalized RNA-seq levels of four genes to which any of these SNPs were mapped, including TLR1 (ENSG00000174125.3), TRL6 (ENSG00000174130.8), TLR10 (ENSG00000174123.6), and FAM114A1 (ENSG00000197712.7). Covariables included three genotyping principle components, 15 peer factors and sex. Based on the number of genes tested, our Bonferroni-corrected significance threshold was P =0.012 (0.05/4 genes). Informed consents were obtaind from all

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Gene: FAM114A1 - family with sequence similarity 114, member A1 - (NCBI)

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