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PCA, ABG, and PA occur in increased frequency in patients with type 1 diabetes and their relatives and are considered \u201cminor\u201d components of forms of autoimmune polyglandular syndrome (APS). A customized radioimmunoprecipitation assay was applied to 6,749 samples from the Type 1 Diabetes Genetics Consortium to measure ATP4A autoreactivity. Autoantibody prevalence was correlated with variants in HLA class II, PTPN22, and CTLA4 genes. With an ATP4A radioimmunoprecipitation assay, PCA were detected in sera from 20.9% of affected individuals. PCA prevalence increased with age and was greater in females (25.3%) than males (16.5%) and among Hispanics (36.3%) and blacks (26.2%) compared with non-Hispanic whites (20.8%) and Asians (16.7%). PCA and other organ-specific autoantibodies GAD65, IA-2, thyroid peroxidase (TPO), 21-hydroxylase (21-OH), and transglutaminase (TG) clustered within families with heritability estimates from 71 to 95%. PCA clustered with TPO, 21-OH, and persistent GAD65 autoantibodies but not with celiac (TG) or IA-2 autoantibodies. PCA-positive subjects showed an increased frequency of DRB1*0404, DPB1*0201, and PTPN22 R620W (rs2476601-T) and a decreased frequency of DRB1*0101, DPB1*0301, and CTLA4 CT60 (rs3087243-T). Genetic variants accounted for 4\u20135% of the heritable risk for PCA. The same alleles were associated with other autoantibody phenotypes in a consistent pattern. Whereas most of the heritable risk for PCA and other antibodies reflects genetic effects that are tissue specific, parietal cell autoimmunity is a major pathogenetic contributor in APS2.<\/jats:p>","DOI":"10.2337\/dcs15-2006","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T19:17:54Z","timestamp":1443122274000},"page":"S29-S36","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":12,"title":["ATPase4A Autoreactivity and Its Association With Autoimmune Phenotypes in the Type 1 Diabetes Genetics Consortium Study"],"prefix":"10.2337","volume":"38","author":[{"given":"Janet M.","family":"Wenzlau","sequence":"first","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela R.","family":"Fain","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Frisch","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Annibale","sequence":"additional","affiliation":[{"name":"Digestive and Liver Disease Unit, University \u201cLa Sapienza,\u201d Sant\u2019Andrea Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Hutton","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2015,9,18]]},"reference":[{"key":"2022031218381769100_B1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1210\/jc.2007-2134","article-title":"Autoimmune gastritis in type 1 diabetes: a clinically oriented review","volume":"93","author":"De Block","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031218381769100_B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/08830180590884413","article-title":"Autoimmune gastritis: historical antecedents, outstanding discoveries, and unresolved problems","volume":"24","author":"Whittingham","year":"2005","journal-title":"Int Rev Immunol"},{"key":"2022031218381769100_B3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.autrev.2011.01.009","article-title":"Pernicious anemia - genetic insights","volume":"10","author":"Banka","year":"2011","journal-title":"Autoimmun Rev"},{"key":"2022031218381769100_B4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/08830180590884404","article-title":"Genetic control of susceptibility to autoimmune gastritis","volume":"24","author":"Baxter","year":"2005","journal-title":"Int Rev Immunol"},{"key":"2022031218381769100_B5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3109\/08916939009041039","article-title":"Are thyrogastric autoantibodies associated with an increased susceptibility to developing type 1 (insulin-dependent) diabetes? 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