{"id":51464,"date":"2024-12-18T14:02:07","date_gmt":"2024-12-18T14:02:07","guid":{"rendered":""},"modified":"2024-12-18T14:02:07","modified_gmt":"2024-12-18T14:02:07","slug":"%d8%aa%d8%b1%d8%ac%d9%85%d9%87-%d9%81%d8%a7%d8%b1%d8%b3%db%8c-%d9%85%d9%82%d8%a7%d9%84%d9%87-51464","status":"publish","type":"product","link":"https:\/\/express24.ir\/d\/product\/%d8%aa%d8%b1%d8%ac%d9%85%d9%87-%d9%81%d8%a7%d8%b1%d8%b3%db%8c-%d9%85%d9%82%d8%a7%d9%84%d9%87-51464\/","title":{"rendered":"\u062a\u0631\u062c\u0645\u0647 \u0641\u0627\u0631\u0633\u06cc \u0645\u0642\u0627\u0644\u0647 \u0627\u062b\u0631\u0627\u062a \u0622\u0644\u0644\u06cc \u0628\u0631 \u0628\u06cc\u0627\u0646 KLHL17 \u0627\u062d\u062a\u0645\u0627\u0644\u0627\u064b \u0628\u0627 \u0648\u0627\u0633\u0637\u0647 JunB\/D \u0632\u0645\u06cc\u0646\u0647 \u0633\u0627\u0632 \u0633\u06cc\u06af\u0646\u0627\u0644 PDAC GWAS \u062f\u0631 chr1p36.33 \u0627\u0633\u062a."},"content":{"rendered":"\n\n\n\n\n\n\n\n\n\n\n\n
\u0639\u0646\u0648\u0627\u0646 \u0645\u0642\u0627\u0644\u0647 \u0628\u0647 \u0627\u0646\u06af\u0644\u06cc\u0633\u06cc <\/td>\nAllelic effects on KLHL17 expression likely mediated by JunB\/D underlie a PDAC GWAS signal at chr1p36.33<\/td>\n<\/tr>\n
\u0639\u0646\u0648\u0627\u0646 \u0645\u0642\u0627\u0644\u0647 \u0628\u0647 \u0641\u0627\u0631\u0633\u06cc <\/td>\n\u062a\u0631\u062c\u0645\u0647 \u0641\u0627\u0631\u0633\u06cc \u0645\u0642\u0627\u0644\u0647 \u0627\u062b\u0631\u0627\u062a \u0622\u0644\u0644\u06cc \u0628\u0631 \u0628\u06cc\u0627\u0646 KLHL17 \u0627\u062d\u062a\u0645\u0627\u0644\u0627\u064b \u0628\u0627 \u0648\u0627\u0633\u0637\u0647 JunB\/D \u0632\u0645\u06cc\u0646\u0647 \u0633\u0627\u0632 \u0633\u06cc\u06af\u0646\u0627\u0644 PDAC GWAS \u062f\u0631 chr1p36.33 \u0627\u0633\u062a.<\/td>\n<\/tr>\n
\u0646\u0648\u06cc\u0633\u0646\u062f\u06af\u0627\u0646 <\/td>\nKatelyn E. Connelly, Katherine Hullin, Ehssan Abdolalizadeh, Jun Zhong, Daina Eiser, Aidan O\u2019Brien, Irene Collins, Sudipto Das, Gerard Duncan, Pancreatic Cancer Cohort Consortium, Pancreatic Cancer Case-Control Consortium, Stephen J. Chanock, Rachael Z. Stolzenberg-Solomon, ProfileAlison P. Klein, Brian M. Wolpin, Jason W. Hoskins, Thorkell Andresson, Jill P. Smith, Laufey T. Amundadottir<\/td>\n<\/tr>\n
\u0641\u0631\u0645\u062a \u0645\u0642\u0627\u0644\u0647 \u0627\u0646\u06af\u0644\u06cc\u0633\u06cc <\/td>\nPDF<\/td>\n<\/tr>\n
\u0632\u0628\u0627\u0646 \u0645\u0642\u0627\u0644\u0647 \u062a\u062d\u0648\u06cc\u0644\u06cc <\/td>\n\u062a\u0631\u062c\u0645\u0647 \u0641\u0627\u0631\u0633\u06cc<\/td>\n<\/tr>\n
\u0641\u0631\u0645\u062a \u0645\u0642\u0627\u0644\u0647 \u062a\u0631\u062c\u0645\u0647 \u0634\u062f\u0647 <\/td>\n\u0628\u0647 \u0635\u0648\u0631\u062a \u0641\u0627\u06cc\u0644 \u0648\u0631\u062f<\/td>\n<\/tr>\n
\u0646\u062d\u0648\u0647 \u062a\u062d\u0648\u06cc\u0644 \u062a\u0631\u062c\u0645\u0647 <\/td>\n\u062f\u0648 \u062a\u0627 \u0633\u0647 \u0631\u0648\u0632 \u067e\u0633 \u0627\u0632 \u062b\u0628\u062a \u0633\u0641\u0627\u0631\u0634 (\u0628\u0647 \u0635\u0648\u0631\u062a \u0641\u0627\u06cc\u0644 \u062f\u0627\u0646\u0644\u0648\u062f\u06cc)<\/td>\n<\/tr>\n
\u062a\u0639\u062f\u0627\u062f \u0635\u0641\u062d\u0627\u062a<\/td>\n26<\/td>\n<\/tr>\n
\u0644\u06cc\u0646\u06a9 \u062f\u0627\u0646\u0644\u0648\u062f \u0631\u0627\u06cc\u06af\u0627\u0646 \u0645\u0642\u0627\u0644\u0647 \u0627\u0646\u06af\u0644\u06cc\u0633\u06cc<\/td>\n\u062f\u0627\u0646\u0644\u0648\u062f \u0645\u0642\u0627\u0644\u0647<\/a><\/td>\n<\/tr>\n
\u062f\u0633\u062a\u0647 \u0628\u0646\u062f\u06cc \u0645\u0648\u0636\u0648\u0639\u0627\u062a <\/td>\nGenetic and Genomic Medicine
\n\u062f\u0627\u0631\u0648\u06cc \u0698\u0646\u062a\u06cc\u06a9\u06cc \u0648 \u0698\u0646\u0648\u0645\u06cc<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\r\n\r\n \r\n \r\n \r\n \r\n
\u0641\u0631\u0645\u062a \u0627\u0631\u0627\u0626\u0647 \u062a\u0631\u062c\u0645\u0647 \u0645\u0642\u0627\u0644\u0647 <\/td>\r\n \u062a\u062d\u0648\u06cc\u0644 \u0628\u0647 \u0635\u0648\u0631\u062a \u0641\u0627\u06cc\u0644 \u0648\u0631\u062f<\/td>\r\n <\/tr>\r\n
\u0632\u0645\u0627\u0646 \u062a\u062d\u0648\u06cc\u0644 \u062a\u0631\u062c\u0645\u0647 \u0645\u0642\u0627\u0644\u0647 <\/td>\r\n \u0628\u06cc\u0646 2 \u062a\u0627 3 \u0631\u0648\u0632 \u067e\u0633 \u0627\u0632 \u062b\u0628\u062a \u0633\u0641\u0627\u0631\u0634<\/td>\r\n <\/tr>\r\n\t
\u06a9\u06cc\u0641\u06cc\u062a \u062a\u0631\u062c\u0645\u0647 <\/td>\r\n \u0628\u0633\u06cc\u0627\u0631 \u0628\u0627\u0644\u0627. \u0645\u0642\u0627\u0644\u0647 \u0641\u0642\u0637 \u062a\u0648\u0633\u0637 \u0645\u062a\u0631\u062c\u0645\u06cc\u0646 \u0628\u0627 \u0645\u062f\u0631\u06a9 \u062f\u0627\u0646\u0634\u06af\u0627\u0647\u06cc \u0645\u062a\u0631\u062c\u0645\u06cc \u062a\u0631\u062c\u0645\u0647 \u0645\u06cc\u200c\u0634\u0648\u062f.<\/td>\r\n <\/tr>\r\n\t\t
\u062c\u062f\u0627\u0648\u0644 \u0648 \u0641\u0631\u0645\u0648\u0644 \u0647\u0627 <\/td>\r\n \u06a9\u0644\u06cc\u0647 \u062c\u062f\u0627\u0648\u0644 \u0648 \u0641\u0631\u0645\u0648\u0644 \u0647\u0627 \u0646\u06cc\u0632 \u062f\u0631 \u0641\u0627\u06cc\u0644 \u062a\u062d\u0648\u06cc\u0644\u06cc \u0648\u0631\u062f \u062f\u0631\u062c \u0645\u06cc\u200c\u0634\u0648\u0646\u062f.<\/td>\r\n <\/tr>\r\n<\/table>\r\n\r\n\n

\u0686\u06a9\u06cc\u062f\u0647<\/h2>\n

Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the U.S. Both rare and common germline variants contribute to PDAC risk. Here, we fine-map and functionally characterize a common PDAC risk signal at 1p36.33 (tagged by rs13303010) identified through a genome wide association study (GWAS). One of the fine-mapped SNPs, rs13303160 (r2=0.93 in 1000G EUR samples, OR=1.23, P value=2.74\u00d710\u22129) demonstrated allele-preferential gene regulatory activity in vitro and allele-preferential binding of JunB and JunD in vitro and in vivo. Expression Quantitative Trait Locus (eQTL) analysis identified KLHL17 as a likely target gene underlying the signal. Proteomic analysis identified KLHL17 as a member of the Cullin-E3 ubiquitin ligase complex in PDAC-derived cells. In silico differential gene expression analysis of the GTExv8 pancreas data suggested an association between lower KLHL17 (risk associated) and pro-inflammatory pathways. We hypothesize that KLHL17 may mitigate inflammation by recruiting pro-inflammatory proteins for ubiquitination and degradation thereby influencing PDAC risk.<\/p>\n

\u0686\u06a9\u06cc\u062f\u0647 \u0628\u0647 \u0641\u0627\u0631\u0633\u06cc (\u062a\u0631\u062c\u0645\u0647 \u0645\u0627\u0634\u06cc\u0646\u06cc)<\/h2>\n

\u0622\u062f\u0646\u0648\u06a9\u0627\u0631\u0633\u06cc\u0646\u0648\u0645\u0627 \u0645\u062c\u0631\u0627\u06cc \u0644\u0648\u0632\u0627\u0644\u0645\u0639\u062f\u0647 (PDAC) \u0633\u0648\u0645\u06cc\u0646 \u0639\u0644\u062a \u0627\u0635\u0644\u06cc \u0645\u0631\u06af \u0648 \u0645\u06cc\u0631 \u0646\u0627\u0634\u06cc \u0627\u0632 \u0633\u0631\u0637\u0627\u0646 \u062f\u0631 \u0627\u06cc\u0627\u0644\u0627\u062a \u0645\u062a\u062d\u062f\u0647 \u0627\u0633\u062a \u06a9\u0647 \u0647\u0631 \u062f\u0648 \u0646\u0648\u0639 \u0698\u0631\u0645\u0646 \u0646\u0627\u062f\u0631 \u0648 \u0645\u0634\u062a\u0631\u06a9 \u0647\u0645 \u062f\u0631 \u062e\u0637\u0631 PDAC \u0646\u0642\u0634 \u062f\u0627\u0631\u0646\u062f.\u062f\u0631 \u0627\u06cc\u0646\u062c\u0627 \u060c \u0645\u0627 \u0646\u0642\u0634\u0647 \u0631\u06cc\u0632 \u0648 \u0628\u0647 \u0635\u0648\u0631\u062a \u0639\u0645\u0644\u06a9\u0631\u062f\u06cc \u06cc\u06a9 \u0633\u06cc\u06af\u0646\u0627\u0644 \u062e\u0637\u0631 PDAC \u0645\u0634\u062a\u0631\u06a9 \u0631\u0627 \u062f\u0631 1P36.33 (\u0628\u0631\u0686\u0633\u0628 RS13303010) \u0645\u0634\u062e\u0635 \u0645\u06cc \u06a9\u0646\u06cc\u0645 \u06a9\u0647 \u0627\u0632 \u0637\u0631\u06cc\u0642 \u06cc\u06a9 \u0645\u0637\u0627\u0644\u0639\u0647 \u0627\u0631\u062a\u0628\u0627\u0637 \u06af\u0633\u062a\u0631\u062f\u0647 \u0698\u0646\u0648\u0645 (GWAS) \u0645\u0634\u062e\u0635 \u0634\u062f\u0647 \u0627\u0633\u062a.\u06cc\u06a9\u06cc \u0627\u0632 SNP \u0647\u0627\u06cc \u0631\u06cc\u0632 \u0648 \u062f\u0631\u0634\u062a \u060c RS13303160 (R2 = 0.93 \u062f\u0631 1000G EUR \u0646\u0645\u0648\u0646\u0647 \u060c OR = 1.23 \u060c \u0645\u0642\u062f\u0627\u0631 P = 2.74 \u00d7 10-9) \u0641\u0639\u0627\u0644\u06cc\u062a \u062a\u0646\u0638\u06cc\u0645 \u06a9\u0646\u0646\u062f\u0647 \u0698\u0646 \u067e\u06cc\u0634\u0641\u0631\u0646\u06cc\u0627\u06cc\u06cc \u0622\u0644\u0644 \u0631\u0627 \u062f\u0631 \u0634\u0631\u0627\u06cc\u0637 \u0622\u0632\u0645\u0627\u06cc\u0634\u06af\u0627\u0647\u06cc \u0648 \u0627\u062a\u0635\u0627\u0644 \u0622\u0644\u0644 \u0627\u0632 JUNB \u0648 JUND \u0646\u0634\u0627\u0646 \u062f\u0627\u062f.in vitro \u0648 in vivo.\u062a\u062c\u0632\u06cc\u0647 \u0648 \u062a\u062d\u0644\u06cc\u0644 \u0645\u06a9\u0627\u0646 \u06a9\u0645\u06cc \u0635\u0641\u062a (EQTL) KLHL17 \u0631\u0627 \u0628\u0647 \u0639\u0646\u0648\u0627\u0646 \u06cc\u06a9 \u0698\u0646 \u0647\u062f\u0641 \u0627\u062d\u062a\u0645\u0627\u0644\u06cc \u0632\u06cc\u0631 \u0633\u06cc\u06af\u0646\u0627\u0644 \u0634\u0646\u0627\u0633\u0627\u06cc\u06cc \u06a9\u0631\u062f.\u062a\u062c\u0632\u06cc\u0647 \u0648 \u062a\u062d\u0644\u06cc\u0644 \u067e\u0631\u0648\u062a\u0626\u0648\u0645\u06cc\u06a9 KLHL17 \u0631\u0627 \u0628\u0647 \u0639\u0646\u0648\u0627\u0646 \u0639\u0636\u0648 \u0645\u062c\u062a\u0645\u0639 \u0644\u06cc\u06af\u0627\u0632 ubiquitin Cullin-E3 \u062f\u0631 \u0633\u0644\u0648\u0644\u0647\u0627\u06cc \u0645\u0634\u062a\u0642 \u0627\u0632 PDAC \u0634\u0646\u0627\u0633\u0627\u06cc\u06cc \u06a9\u0631\u062f.\u062f\u0631 \u062a\u062c\u0632\u06cc\u0647 \u0648 \u062a\u062d\u0644\u06cc\u0644 \u0628\u06cc\u0627\u0646 \u0698\u0646 \u062f\u06cc\u0641\u0631\u0627\u0646\u0633\u06cc\u0644 \u0633\u06cc\u0644\u06cc\u06a9\u0648 \u0627\u0632 \u062f\u0627\u062f\u0647 \u0647\u0627\u06cc \u0644\u0648\u0632\u0627\u0644\u0645\u0639\u062f\u0647 GTEXV8 \u060c \u0627\u0631\u062a\u0628\u0627\u0637 \u0628\u06cc\u0646 KLHL17 \u067e\u0627\u06cc\u06cc\u0646 \u062a\u0631 (\u062e\u0637\u0631 \u0645\u0631\u062a\u0628\u0637 \u0628\u0627 \u062e\u0637\u0631) \u0648 \u0645\u0633\u06cc\u0631\u0647\u0627\u06cc \u0627\u0644\u062a\u0647\u0627\u0628\u06cc \u0631\u0627 \u0646\u0634\u0627\u0646 \u0645\u06cc \u062f\u0647\u062f.\u0645\u0627 \u0641\u0631\u0636 \u0645\u06cc \u06a9\u0646\u06cc\u0645 \u06a9\u0647 KLHL17 \u0645\u0645\u06a9\u0646 \u0627\u0633\u062a \u0628\u0627 \u062c\u0630\u0628 \u067e\u0631\u0648\u062a\u0626\u06cc\u0646 \u0647\u0627\u06cc \u0627\u0644\u062a\u0647\u0627\u0628\u06cc \u0628\u0631\u0627\u06cc \u0647\u0645\u0647 \u06af\u06cc\u0631 \u0648 \u062a\u062e\u0631\u06cc\u0628 \u062f\u0631 \u0646\u062a\u06cc\u062c\u0647 \u0628\u0631 \u062e\u0637\u0631 PDAC \u060c \u0627\u0644\u062a\u0647\u0627\u0628 \u0631\u0627 \u06a9\u0627\u0647\u0634 \u062f\u0647\u062f.<\/p>\n\r\n\r\n \r\n \r\n \r\n \r\n
\u0641\u0631\u0645\u062a \u0627\u0631\u0627\u0626\u0647 \u062a\u0631\u062c\u0645\u0647 \u0645\u0642\u0627\u0644\u0647 <\/td>\r\n \u062a\u062d\u0648\u06cc\u0644 \u0628\u0647 \u0635\u0648\u0631\u062a \u0641\u0627\u06cc\u0644 \u0648\u0631\u062f<\/td>\r\n <\/tr>\r\n
\u0632\u0645\u0627\u0646 \u062a\u062d\u0648\u06cc\u0644 \u062a\u0631\u062c\u0645\u0647 \u0645\u0642\u0627\u0644\u0647 <\/td>\r\n \u0628\u06cc\u0646 2 \u062a\u0627 3 \u0631\u0648\u0632 \u067e\u0633 \u0627\u0632 \u062b\u0628\u062a \u0633\u0641\u0627\u0631\u0634<\/td>\r\n <\/tr>\r\n\t
\u06a9\u06cc\u0641\u06cc\u062a \u062a\u0631\u062c\u0645\u0647 <\/td>\r\n \u0628\u0633\u06cc\u0627\u0631 \u0628\u0627\u0644\u0627. \u0645\u0642\u0627\u0644\u0647 \u0641\u0642\u0637 \u062a\u0648\u0633\u0637 \u0645\u062a\u0631\u062c\u0645\u06cc\u0646 \u0628\u0627 \u0645\u062f\u0631\u06a9 \u062f\u0627\u0646\u0634\u06af\u0627\u0647\u06cc \u0645\u062a\u0631\u062c\u0645\u06cc \u062a\u0631\u062c\u0645\u0647 \u0645\u06cc\u200c\u0634\u0648\u062f.<\/td>\r\n <\/tr>\r\n\t\t
\u062c\u062f\u0627\u0648\u0644 \u0648 \u0641\u0631\u0645\u0648\u0644 \u0647\u0627 <\/td>\r\n \u06a9\u0644\u06cc\u0647 \u062c\u062f\u0627\u0648\u0644 \u0648 \u0641\u0631\u0645\u0648\u0644 \u0647\u0627 \u0646\u06cc\u0632 \u062f\u0631 \u0641\u0627\u06cc\u0644 \u062a\u062d\u0648\u06cc\u0644\u06cc \u0648\u0631\u062f \u062f\u0631\u062c \u0645\u06cc\u200c\u0634\u0648\u0646\u062f.<\/td>\r\n <\/tr>\r\n<\/table>\r\n\r\n\n","protected":false},"excerpt":{"rendered":"

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