Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures.

Humans Celiac Disease / genetics Female Autoimmunity / genetics Male Environmental Exposure / adverse effects Child, Preschool Polymorphism, Single Nucleotide Child Genetic Predisposition to Disease Seasons CD3 Complex / genetics Infant Risk Factors Gene-Environment Interaction Protein Glutamine gamma Glutamyltransferase 2 Prospective Studies Birth Cohort

Journal

Scientific reports

ISSN: 2045-2322

Titre abrégé: Sci Rep

Pays: England

ID NLM: 101563288

Informations de publication

Date de publication:
26 Oct 2024

Historique:

received: 14 02 2024

accepted: 07 10 2024

medline: 27 10 2024

pubmed: 27 10 2024

entrez: 27 10 2024

Statut: epublish

Résumé

Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study. Altogether 6523 genetically predisposed children were enrolled to long-term follow-up with prospective sampling and data collection at six research centers in the USA, Germany, Sweden and Finland. Celiac disease autoimmunity was defined as positive tissue transglutaminase antibodies in two consecutive serum samples. There was a significant season of birth effect on the risk of celiac autoimmunity. The effect was dependent on polymorphisms in CD247 gene encoding for CD3ζ chain of TCR-CD3 complex. In particular, children with major alleles for SNP rs864537A > G, in CD247 (AA genotype) had an excess risk of celiac autoimmunity when born March-August as compared to other months. The interaction of CD247 with season of birth on autoimmunity risk was accompanied by interactions with febrile infections between the ages of 3-6 months. Considering the important role of TCR-CD3 complex in the adaptive immune response and our findings here, CD247 variants and their possible effect of subgroups in autoimmunity development could be of interest in the design of future gene-environment studies of celiac disease. ClinicalTrials.gov Identifier: NCT00279318.

Identifiants

DOI: 10.1038/s41598-024-75496-w PMID: 39462122

pubmed: 39462122

doi: 10.1038/s41598-024-75496-w

pii: 10.1038/s41598-024-75496-w

doi:

Substances chimiques

CD3 Complex 0

Protein Glutamine gamma Glutamyltransferase 2 EC 2.3.2.13

Banques de données

ClinicalTrials.gov

['NCT00279318']

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

Pagination

25463

Investigateurs

Marian Rewers (M)

Aaron Barbour (A)

Kimberly Bautista (K)

Judith Baxter (J)

Daniel Felipe-Morales (D)

Brigitte I Frohnert (BI)

Marisa Stahl (M)

Patricia Gesualdo (P)

Michelle Hoffman (M)

Rachel Karban (R)

Edwin Liu (E)

Alondra Munoz (A)

Jill Norris (J)

Holly O'Donnell (H)

Stesha Peacock (S)

Hanan Shorrosh (H)

Andrea Steck (A)

Megan Stern (M)

Kathleen Waugh (K)

Jorma Toppari (J)

Olli G Simell (OG)

Annika Adamsson (A)

Suvi Ahonen (S)

Mari Åkerlund (M)

Sirpa Anttila (S)

Leena Hakola (L)

Anne Hekkala (A)

Tiia Honkanen (T)

Heikki Hyöty (H)

Jorma Ilonen (J)

Sanna Jokipuu (S)

Taru Karjalainen (T)

Leena Karlsson (L)

Jukka Kero (J)

Jaakko J Koskenniemi (JJ)

Miia Kähönen (M)

Mikael Knip (M)

Minna-Liisa Koivikko (ML)

Katja Kokkonen (K)

Merja Koskinen (M)

Mirva Koreasalo (M)

Kalle Kurppa (K)

Salla Kuusela (S)

Jutta Laiho (J)

Tiina Latva-Aho (T)

Laura Leppänen (L)

Katri Lindfors (K)

Maria Lönnrot (M)

Elina Mäntymäki (E)

Markus Mattila (M)

Maija Miettinen (M)

Teija Mykkänen (T)

Tiina Niininen (T)

Sari Niinistö (S)

Sami Oikarinen (S)

Hanna-Leena Oinas (HL)

Paula Ollikainen (P)

Zhian Othmani (Z)

Aino Pitkänen (A)

Sirpa Pohjola (S)

Jenna Rautanen (J)

Anne Riikonen (A)

Minna Romo (M)

Nelli Rönkä (N)

Satu Simell (S)

Päivi Tossavainen (P)

Mari Vähä-Mäkilä (M)

Eeva Varjonen (E)

Riitta Veijola (R)

Irene Viinikangas (I)

Silja Vilmi (S)

Suvi M Virtanen (SM)

Richard McIndoe (R)

Desmond Schatz (D)

Diane Hopkins (D)

Michael Haller (M)

Risa Bernard (R)

Melissa Gardiner (M)

Ashok Sharma (A)

Laura Jacobsen (L)

Ashley DePeiza (A)

Jennifer Hosford (J)

Kennedy Petty (K)

Leah Myers (L)

Anette Ziegler (A)

Ezio Bonifacio (E)

Cigdem Gezginci (C)

Willi Grätz (W)

Anja Heublein (A)

Eva Hohoff (E)

Sandra Hummel (S)

Annette Knopff (A)

Melanie Köger (M)

Sibylle Koletzko (S)

Claudia Ramminger (C)

Roswith Roth (R)

Jennifer Schmidt (J)

Marlon Scholz (M)

Joanna Stock (J)

Katharina Warncke (K)

Lorena Wendel (L)

Christiane Winkler (C)

Åke Lernmark (Å)

Daniel Agardh (D)

Carin Andrén Aronsson (CA)

Rasmus Bennet (R)

Corrado Cilio (C)

Susanne Dahlberg (S)

Ulla Fält (U)

Malin Goldman Tsubarah (MG)

Emelie Ericson-Hallström (E)

Lina Fransson (L)

Thomas Gard (T)

Emina Halilovic (E)

Gunilla Holmén (G)

Susanne Hyberg (S)

Berglind Jonsdottir (B)

Naghmeh Karimi (N)

Helena Elding Larsson (HE)

Marielle Lindström (M)

Markus Lundgren (M)

Marlena Maziarz (M)

Jessica Melin (J)

Caroline Nilsson (C)

Yohanna Nordh (Y)

Kobra Rahmati (K)

Anita Ramelius (A)

Falastin Salami (F)

Anette Sjöberg (A)

Evelyn Tekum Amboh Carina Törn (ETAC)

Ulrika Ulvenhag (U)

Terese Wiktorsson (T)

Åsa Wimar (Å)

William A Hagopian (WA)

Michael Killian (M)

Claire Cowen Crouch (CC)

Jennifer Skidmore (J)

Luka-Sophia Bowen (LS)

Mikeil Metcalf (M)

Arlene Meyer (A)

Jocelyn Meyer (J)

Denise Mulenga (D)

Nole Powell (N)

Jared Radtke (J)

Shreya Roy (S)

Davey Schmitt (D)

Preston Tucker (P)

Dorothy Becker (D)

Margaret Franciscus (M)

MaryEllen Dalmagro-Elias Smith (MD)

Ashi Daftary (A)

Mary Beth Klein (MB)

Chrystal Yates (C)

Jeffrey Krischer (J)

Rajesh Adusumali (R)

Sarah Austin-Gonzalez (S)

Maryouri Avendano (M)

Sandra Baethke (S)

Brant Burkhardt (B)

Martha Butterworth (M)

Nicholas Cadigan (N)

Joanna Clasen (J)

Kevin Counts (K)

Laura Gandolfo (L)

Jennifer Garmeson (J)

Veena Gowda (V)

Christina Karges (C)

Shu Liu (S)

Xiang Liu (X)

Kristian Lynch (K)

Jamie Malloy (J)

Lazarus Mramba (L)

Cristina McCarthy (C)

Jose Moreno (J)

Hemang Parikh (H)

Cassandra Remedios (C)

Chris Shaffer (C)

Susan Smith (S)

Noah Sulman (N)

Roy Tamura (R)

Dena Tewey (D)

Henri Thuma (H)

Michael Toth (M)

Ulla Uusitalo (U)

Kendra Vehik (K)

Ponni Vijayakandipan (P)

Melissa Wroble (M)

Jimin Yang (J)

Kenneth Young (K)

Michael Abbondondolo (M)

Lori Ballard (L)

Rasheedah Brown (R)

David Cuthbertson (D)

Stephen Dankyi (S)

Christopher Eberhard (C)

Steven Fiske (S)

David Hadley (D)

Kathleen Heyman (K)

Belinda Hsiao (B)

Francisco Perez Laras (FP)

Hye-Seung Lee (HS)

Qian Li (Q)

Colleen Maguire (C)

Wendy McLeod (W)

Aubrie Merrell (A)

Steven Meulemans (S)

Ryan Quigley (R)

Laura Smith (L)

Beena Akolkar (B)

Liping Yu (L)

Dongmei Miao (D)

Kathleen Gillespie (K)

Kyla Chandler (K)

Ilana Kelland (I)

Yassin Ben Khoud (YB)

Matthew Randell (M)

Stephen S Rich (SS)

Wei-Min Chen (WM)

Suna Onengut-Gumuscu (S)

Emily Farber (E)

Rebecca Roche Pickin (RR)

Jonathan Davis (J)

Jordan Davis (J)

Dan Gallo (D)

Jessica Bonnie (J)

Paul Campolieto (P)

William Hagopian (W)

Jared Radtke (J)

Preston Tucker (P)

Henry Erlich (H)

Steven J Mack (SJ)

Anna Lisa Fear (AL)

Sandra Ke (S)

Niveen Mulholland (N)

Thomas Briese (T)

Todd Brusko (T)

Suzanne Bennett Johnson (SB)

Eoin McKinney (E)

Tomi Pastinen (T)

Steffen Ullitz Thorsen (SU)

Eric Triplett (E)

Informations de copyright

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