Matches in SemOpenAlex for { <https://semopenalex.org/work/W2788587725> ?p ?o ?g. }
- W2788587725 endingPage "2177" @default.
- W2788587725 startingPage "2165" @default.
- W2788587725 abstract "Background & AimsA few rare monogenic primary immunodeficiencies (PIDs) are characterized by chronic intestinal inflammation that resembles Crohn’s disease (CD). We investigated whether 23 genes associated with 10 of these monogenic disorders contain common, low-frequency, or rare variants that increase risk for CD.MethodsCommon and low frequency variants in 1 Mb loci centered on the candidate genes were analyzed using meta-data corresponding to genotypes of approximately 17,000 patients with CD or without CD (controls) in Europe. The contribution of rare variants was assessed by high-throughput sequencing of 4750 individuals, including 660 early-onset and/or familial cases among the 2390 patients with CD. Variants were expressed from vectors in SW480 or HeLa cells and functions of their products were analyzed in immunofluorescence, luciferase, immunoprecipitation, and immunoblot assays.ResultsWe reproduced the association of the interleukin 10 locus with CD (P = .007), although none of the significantly associated variants modified the coding sequence of interleukin 10. We found XIAP to be significantly enriched for rare coding mutations in patients with CD vs controls (P = .02). We identified 4 previously unreported missense variants associated with CD. Variants in XIAP cause the PID X-linked lymphoproliferative disease type 2, yet none of the carriers of these variants had all the clinical features of X-linked lymphoproliferative disease type 2. Identified XIAP variants S123N, R233Q, and P257A were associated with an impaired activation of NOD2 signaling after muramyl dipeptide stimulation.ConclusionsIn a systematic analysis of variants in 23 PID-associated genes, we confirmed the association of variants in XIAP with CD. Further screenings for CD-associated variants and analyses of their functions could increase our understanding of the relationship between PID-associated genes and CD pathogenesis. A few rare monogenic primary immunodeficiencies (PIDs) are characterized by chronic intestinal inflammation that resembles Crohn’s disease (CD). We investigated whether 23 genes associated with 10 of these monogenic disorders contain common, low-frequency, or rare variants that increase risk for CD. Common and low frequency variants in 1 Mb loci centered on the candidate genes were analyzed using meta-data corresponding to genotypes of approximately 17,000 patients with CD or without CD (controls) in Europe. The contribution of rare variants was assessed by high-throughput sequencing of 4750 individuals, including 660 early-onset and/or familial cases among the 2390 patients with CD. Variants were expressed from vectors in SW480 or HeLa cells and functions of their products were analyzed in immunofluorescence, luciferase, immunoprecipitation, and immunoblot assays. We reproduced the association of the interleukin 10 locus with CD (P = .007), although none of the significantly associated variants modified the coding sequence of interleukin 10. We found XIAP to be significantly enriched for rare coding mutations in patients with CD vs controls (P = .02). We identified 4 previously unreported missense variants associated with CD. Variants in XIAP cause the PID X-linked lymphoproliferative disease type 2, yet none of the carriers of these variants had all the clinical features of X-linked lymphoproliferative disease type 2. Identified XIAP variants S123N, R233Q, and P257A were associated with an impaired activation of NOD2 signaling after muramyl dipeptide stimulation. In a systematic analysis of variants in 23 PID-associated genes, we confirmed the association of variants in XIAP with CD. Further screenings for CD-associated variants and analyses of their functions could increase our understanding of the relationship between PID-associated genes and CD pathogenesis." @default.
- W2788587725 created "2018-03-06" @default.
- W2788587725 creator A5000851530 @default.
- W2788587725 creator A5004181807 @default.
- W2788587725 creator A5005038496 @default.
- W2788587725 creator A5006016461 @default.
- W2788587725 creator A5014101665 @default.
- W2788587725 creator A5019474609 @default.
- W2788587725 creator A5022014006 @default.
- W2788587725 creator A5022849571 @default.
- W2788587725 creator A5023148106 @default.
- W2788587725 creator A5026868068 @default.
- W2788587725 creator A5029097636 @default.
- W2788587725 creator A5029751505 @default.
- W2788587725 creator A5031594416 @default.
- W2788587725 creator A5042564659 @default.
- W2788587725 creator A5046545260 @default.
- W2788587725 creator A5049113823 @default.
- W2788587725 creator A5056371371 @default.
- W2788587725 creator A5057074793 @default.
- W2788587725 creator A5057622587 @default.
- W2788587725 creator A5059982639 @default.
- W2788587725 creator A5066985999 @default.
- W2788587725 creator A5068262373 @default.
- W2788587725 creator A5068927290 @default.
- W2788587725 creator A5069781760 @default.
- W2788587725 creator A5074139314 @default.
- W2788587725 creator A5074973098 @default.
- W2788587725 creator A5076767319 @default.
- W2788587725 creator A5077220554 @default.
- W2788587725 creator A5082765432 @default.
- W2788587725 creator A5083175269 @default.
- W2788587725 creator A5086041686 @default.
- W2788587725 creator A5089852959 @default.
- W2788587725 date "2018-06-01" @default.
- W2788587725 modified "2023-10-16" @default.
- W2788587725 title "Analysis of Genes Associated With Monogenic Primary Immunodeficiency Identifies Rare Variants in XIAP in Patients With Crohn’s Disease" @default.
- W2788587725 cites W1014257459 @default.
- W2788587725 cites W1492798098 @default.
- W2788587725 cites W1506286232 @default.
- W2788587725 cites W1563940013 @default.
- W2788587725 cites W1919257374 @default.
- W2788587725 cites W1980740976 @default.
- W2788587725 cites W1983117044 @default.
- W2788587725 cites W1987425031 @default.
- W2788587725 cites W1991354637 @default.
- W2788587725 cites W1992436001 @default.
- W2788587725 cites W1995197668 @default.
- W2788587725 cites W1998642504 @default.
- W2788587725 cites W2004451243 @default.
- W2788587725 cites W2008342326 @default.
- W2788587725 cites W2012697072 @default.
- W2788587725 cites W2019232525 @default.
- W2788587725 cites W2020040634 @default.
- W2788587725 cites W2038753879 @default.
- W2788587725 cites W2043897018 @default.
- W2788587725 cites W2045870813 @default.
- W2788587725 cites W2056852317 @default.
- W2788587725 cites W2059632816 @default.
- W2788587725 cites W2062862675 @default.
- W2788587725 cites W2066835641 @default.
- W2788587725 cites W2067256947 @default.
- W2788587725 cites W2071988911 @default.
- W2788587725 cites W2072025083 @default.
- W2788587725 cites W2075045888 @default.
- W2788587725 cites W2078621117 @default.
- W2788587725 cites W2087587407 @default.
- W2788587725 cites W2089454467 @default.
- W2788587725 cites W2097903730 @default.
- W2788587725 cites W2102865263 @default.
- W2788587725 cites W2106779017 @default.
- W2788587725 cites W2108135154 @default.
- W2788587725 cites W2116432220 @default.
- W2788587725 cites W2118300504 @default.
- W2788587725 cites W2119067354 @default.
- W2788587725 cites W2122031852 @default.
- W2788587725 cites W2123123035 @default.
- W2788587725 cites W2127303484 @default.
- W2788587725 cites W2127315968 @default.
- W2788587725 cites W2135199713 @default.
- W2788587725 cites W2139198631 @default.
- W2788587725 cites W2140331116 @default.
- W2788587725 cites W2141820415 @default.
- W2788587725 cites W2143625465 @default.
- W2788587725 cites W2143992683 @default.
- W2788587725 cites W2145382951 @default.
- W2788587725 cites W2147698885 @default.
- W2788587725 cites W2151372766 @default.
- W2788587725 cites W2153210191 @default.
- W2788587725 cites W2153915282 @default.
- W2788587725 cites W2161633633 @default.
- W2788587725 cites W2164046385 @default.
- W2788587725 cites W2164344962 @default.
- W2788587725 cites W2167190329 @default.
- W2788587725 cites W2168030198 @default.
- W2788587725 cites W2182770341 @default.
- W2788587725 cites W2198849031 @default.
- W2788587725 cites W2557981253 @default.