{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:28:54Z","timestamp":1791872934808,"version":"4.3.4"},"reference-count":44,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2010,12,20]]},"published-print":{"date-parts":[[2011,8]]},"abstract":"\n Objective<\/jats:title>\n Genome-wide association studies have identified multiple Crohn's disease (CD) susceptibility loci, including association with non-coding intergenic single-nucleotide polymorphisms (SNPs) at 10q21.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n To fine-map the 10q21 locus, the authors genotyped 86 SNPs in 1632 CD cases and 961 controls and performed single-marker and conditional analyses using logistic regression.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Association with CD risk spanning 11 SNPs (p<0.001) was observed. The most significant association observed was at the non-synonymous SNP, rs7076156 (Ala62Thr), in\n ZNF365<\/jats:italic>\n . The alanine allele was over-represented in CD (p=5.23\u00d710\n \u22127<\/jats:sup>\n ; OR=1.39 (95% CI 1.22 to 1.58)); allele frequency of 76% in CD and 69.7% in controls). Conditional analysis on rs7076156 nullified all other significant associations, suggesting that this is the causative variant at this locus. Four isoforms of\n ZNF365<\/jats:italic>\n have previously been identified, and rs7076156 is located in an exon unique to\n ZNF365<\/jats:italic>\n isoform D. The authors demonstrated, using reverse transcription-PCR, expression of ZNF365D in intestinal resections from both CD subjects and controls. Markedly reduced mean expression levels of ZNF365D were identified in Epstein\u2013Barr virus-transformed lymphoblastoid cell lines from CD subjects homozygous for the risk allele (Ala). A whole-genome microarray expression study further suggested that the Ala62Thr change in\n ZNF365<\/jats:italic>\n isoform D is related to differential expression of the genes\n ARL4A<\/jats:italic>\n ,\n MKKS<\/jats:italic>\n ,\n RRAGD<\/jats:italic>\n ,\n SUMF2<\/jats:italic>\n ,\n TDR1<\/jats:italic>\n and\n ZNF148<\/jats:italic>\n in CD.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Collectively, these data support the hypothesis that the non-synonymous Ala62Thr SNP, rs7076156, underlies the association between 10q21 and CD risk and suggest that this SNP acts by altering expression of genes under the control of\n ZNF365<\/jats:italic>\n isoform D.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/gut.2010.227256","type":"journal-article","created":{"date-parts":[[2011,1,22]],"date-time":"2011-01-22T00:39:24Z","timestamp":1295656764000},"page":"1060-1067","source":"Crossref","is-referenced-by-count":26,"title":["Variants in\n ZNF365<\/i>\n isoform D are associated with 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