{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:15:33Z","timestamp":1790673333676,"version":"4.1.0"},"reference-count":79,"publisher":"American Society for Clinical Investigation","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,23]]},"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Morphological patterns of Paneth cells are a prognostic biomarker in Western Crohn\u2019s disease (CD) patients, and are associated with autophagy-associated\n                    <jats:italic>ATG16L1<\/jats:italic>\n                    and\n                    <jats:italic>NOD2<\/jats:italic>\n                    variants. We hypothesized that genetic determinants of Paneth cell phenotype in other ethnic CD cohorts are distinct but also involved in autophagy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    We performed a hypothesis-driven analysis of 56 single nucleotide polymorphisms (SNPs) associated with CD susceptibility or known to affect Paneth cell function in 110 Japanese CD patients who underwent ileal resection. We subsequently performed a genome-wide association analysis. Paneth cell phenotype was determined by defensin-5 immunofluorescence. Selected genotype\u2013Paneth cell defect correlations were compared to a Western CD cohort (\n                    <jats:italic>n<\/jats:italic>\n                    = 164).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    The average percentage of abnormal Paneth cells in Japanese CD was similar to Western CD (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.87), and abnormal Paneth cell phenotype was also associated with early recurrence (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.013). In contrast to Western CD,\n                    <jats:italic>ATG16L1<\/jats:italic>\n                    T300A was not associated with Paneth cell defect in Japanese CD (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.20). Among the 56 selected SNPs, only\n                    <jats:italic>LRRK2<\/jats:italic>\n                    M2397T showed significant association with Paneth cell defect (\n                    <jats:italic>P<\/jats:italic>\n                    = 3.62 \u00d7 10\n                    <jats:sup>\u20134<\/jats:sup>\n                    ), whereas in the Western CD cohort it was not (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.76). Pathway analysis of\n                    <jats:italic>LRRK2<\/jats:italic>\n                    and other candidate genes with\n                    <jats:italic>P<\/jats:italic>\n                    less than 5 \u00d7 10\n                    <jats:sup>\u20134<\/jats:sup>\n                    showed connections with known CD susceptibility genes and links to autophagy and TNF-\u03b1 networks.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSIONS.<\/jats:bold>\n                    We found dichotomous effects of\n                    <jats:italic>ATG16L1<\/jats:italic>\n                    and\n                    <jats:italic>LRRK2<\/jats:italic>\n                    on Paneth cell defect between Japanese and Western CD. Genes affecting Paneth cell phenotype in Japanese CD were also associated with autophagy. Paneth cell phenotype also predicted prognosis in Japanese CD.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>FUNDING.<\/jats:bold>\n                    Helmsley Charitable Trust, Doris Duke Foundation (grant 2014103), Japan Society for the Promotion of Science (KAKENHI grants JP15H04805 and JP15K15284), Crohn\u2019s and Colitis Foundation grant 274415, NIH (grants 1R56DK095820, K01DK109081, and UL1 TR000448).\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.91917","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T11:01:42Z","timestamp":1490180502000},"source":"Crossref","is-referenced-by-count":56,"title":["LRRK2 but not ATG16L1 is associated with Paneth cell defect in Japanese Crohn\u2019s disease patients"],"prefix":"10.1172","volume":"2","author":[{"given":"Ta-Chiang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Naito","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1535-4322","authenticated-orcid":true,"given":"Zhenqiu","family":"Liu","sequence":"additional","affiliation":[{"name":"F. 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