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Genome-wide association study identifies two novel regions at 11p15.5-p13 and 1p31 with major impact on acute-phase serum amyloid a
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نویسنده
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marzi c. ,albrecht e. ,hysi p.g. ,lagou v. ,waldenberger m. ,tönjes a. ,prokopenko i. ,heim k. ,blackburn h. ,ried j.s. ,kleber m.e. ,mangino m. ,thorand b. ,peters a. ,hammond c.j. ,grallert h. ,boehm b.o. ,kovacs p. ,geistlinger l. ,prokisch h. ,winkelmann b.r. ,spector t.d. ,wichmann h. ,stumvoll m. ,soranzo n. ,märz w. ,koenig w. ,illig t. ,gieger c.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 11
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چکیده
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Elevated levels of acute-phase serum amyloid a (a-saa) cause amyloidosis and are a risk factor for atherosclerosis and its clinical complications,type 2 diabetes,as well as various malignancies. to investigate the genetic basis of a-saa levels,we conducted the first genome-wide association study on baseline a-saa concentrations in three population-based studies (kora,twinsuk,sorbs) and one prospective case cohort study (luric),including a total of 4,212 participants of european descent,and identified two novel genetic susceptibility regions at 11p15.5-p13 and 1p31. the region at 11p15.5-p13 (rs4150642; p = 3.20 × 10-111) contains serum amyloid a1 (saa1) and the adjacent general transcription factor 2 h1 (gtf2h1),hermansky-pudlak syndrome 5 (hps5),lactate dehydrogenase a (ldha),and lactate dehydrogenase c (ldhc). this region explains 10.84% of the total variation of a-saa levels in our data,which makes up 18.37% of the total estimated heritability. the second region encloses the leptin receptor (lepr) gene at 1p31 (rs12753193; p = 1.22 × 10-11) and has been found to be associated with crp and fibrinogen in previous studies. our findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline a-saa levels and provide confirmative evidence of the importance of the 1p31 region for inflammatory processes and the close interplay between a-saa,leptin,and other acute-phase proteins. © 2010 marzi et al.
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آدرس
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institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, oxford centre for diabetes,endocrinology,and metabolism,university of oxford,oxford,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, department of medicine,university of leipzig,leipzig,germany,coordination centre for clinical trials,university of leipzig,leipzig, Germany, oxford centre for diabetes,endocrinology,and metabolism,university of oxford,oxford,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, institute of human genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, wellcome trust sanger institute genome campus,hinxton, United Kingdom, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, luric,freiburg, Germany, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, division of endocrinology,department of medicine,university of ulm,ulm, Germany, interdisciplinary centre for clinical research,department of internal medicine iii,university of leipzig,leipzig, Germany, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, institute of human genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,institute of human genetics,klinikum rechts der isar,technische universität münchen,munich, Germany, cardiology group sachsenhausen,frankfurt, Germany, department of twin research and genetic epidemiology,king's college london,london, United Kingdom, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,institute of medical informatics,biometry and epidemiology,chair of epidemiology,ludwig-maximilians-universität,munich,germany,klinikum grosshadern,munich, Germany, department of medicine,university of leipzig,leipzig, Germany, department of twin research and genetic epidemiology,king's college london,london,united kingdom,wellcome trust sanger institute genome campus,hinxton, United Kingdom, synlab medizinisches versorgungszentrum heidelberg,eppelheim,germany,institut für public health,sozialmedizin und epidemiologie,medizinische fakultät mannheim der universität heidelberg,mannheim,germany,clinical institute of medical and chemical laboratory diagnostics,graz, Austria, department of internal medicine ii - cardiology,university of ulm medical center,ulm, Germany, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany
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Authors
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