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The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove
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نویسنده
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tang m. ,lautenberger j.a. ,gao x. ,sezgin e. ,hendrickson s.l. ,troyer j.l. ,david v.a. ,guan l. ,mcintosh c.e. ,guo x. ,zheng y. ,liao j. ,deng h. ,malasky m. ,kessing b. ,winkler c.a. ,carrington m. ,dé the g. ,zeng y. ,o'brien s.j.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 11
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چکیده
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Nasopharyngeal carcinoma (npc) is an epithelial malignancy facilitated by epstein-barr virus infection. here we resolve the major genetic influences for npc incidence using a genome-wide association study (gwas),independent cohort replication,and high-resolution molecular hla class i gene typing including 4,055 study participants from the guangxi zhuang autonomous region and guangdong province of southern china. we detect and replicate strong association signals involving snps,hla alleles,and amino acid (aa) variants across the major histocompatibility complex-hla-a,hla -b,and hla -c class i genes (phla-a-aa-site-62 = 7.4×10-29; p hla-b-aa-site-116 = 6.5×10-19; p hla-c-aa-site-156 = 6.8×10-8 respectively). over 250 npc-hla associated variants within hla were analyzed in concert to resolve separate and largely independent hla-a,-b,and -c gene influences. multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (or2h1,gabbr1,hla-f,and hcg9) as proxies for peptide binding motifs carried by hla- a*11:01. a similar analysis resolved an independent association signal driven by hla-b*13:01,b*38:02,and b*55:02 alleles together. npc resistance alleles carrying the strongly associated amino acid variants implicate specific class i peptide recognition motifs in hla-a and -b peptide binding groove as conferring strong genetic influence on the development of npc in china.
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آدرس
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college of life science and bio-engineering,beijing university of technology,beijing,china,laboratory of genomic diversity,national cancer institute,frederick,md,united states,wuzhou health system key laboratory for nasopharyngeal carcinoma etiology and molecular mechanism,wuzhou red cross hospital,guangxi, China, bsp-ccr genetics core,frederick national laboratory for cancer research,frederick,md, United States, cancer and inflammation program,laboratory of experimental immunology,saic-frederick,frederick national lab,frederick,md,united states,ragon institute of mgh,mit,and harvard,boston,ma, United States, laboratory of genomic diversity,national cancer institute,frederick,md, United States, department of biology,shepherd university,shepherdstown,wv, United States, laboratory of genomic diversity,saic-frederick,nci-frederick,frederick,md, United States, laboratory of genomic diversity,national cancer institute,frederick,md, United States, laboratory of genomic diversity,saic-frederick,nci-frederick,frederick,md, United States, laboratory of genomic diversity,saic-frederick,nci-frederick,frederick,md, United States, laboratory of genomic diversity,saic-frederick,nci-frederick,frederick,md,united states,state key laboratory for infectious diseases prevention and control,institute for viral disease control and prevention,chinese center for disease control and prevention,beijing, China, wuzhou health system key laboratory for nasopharyngeal carcinoma etiology and molecular mechanism,wuzhou red cross hospital,guangxi, China, department of epidemiology,cangwu institute for nasopharyngeal carcinoma control and prevention,guangxi, China, wuzhou health system key laboratory for nasopharyngeal carcinoma etiology and molecular mechanism,wuzhou red cross hospital,guangxi, China, laboratory of genomic diversity,saic-frederick,nci-frederick,frederick,md, United States, bsp-ccr genetics core,frederick national laboratory for cancer research,frederick,md, United States, laboratory of genomic diversity,saic-frederick,nci-frederick,frederick,md, United States, cancer and inflammation program,laboratory of experimental immunology,saic-frederick,frederick national lab,frederick,md, United States, oncogenic virus epidemiology and pathophysiology,institute pasteur,paris, France, college of life science and bio-engineering,beijing university of technology,beijing,china,state key laboratory for infectious diseases prevention and control,institute for viral disease control and prevention,chinese center for disease control and prevention,beijing, China, laboratory of genomic diversity,national cancer institute,frederick,md, United States
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Authors
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