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Four novel loci (19q13,6q24,12q24,and 5q14) influence the microcirculation in vivo
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نویسنده
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kamran ikram m. ,xueling s. ,jensen r.a. ,cotch m.f. ,hewitt a.w. ,ikram m.a. ,wang j.j. ,klein r. ,klein b.e.k. ,breteler m.m.b. ,cheung n. ,liew g. ,mitchell p. ,uitterlinden a.g. ,rivadeneira f. ,hofman a. ,de jong p.t.v.m. ,van duijn c.m. ,kao l. ,cheng c.-y. ,smith a.v. ,glazer n.l. ,lumley t. ,mcknight b. ,psaty b.m. ,jonasson f. ,eiriksdottir g. ,aspelund t. ,harris t.b. ,launer l.j. ,taylor k.d. ,li x. ,iyengar s.k. ,xi q. ,sivakumaran t.a. ,mackey d.a. ,macgregor s. ,martin n.g. ,young t.l. ,bis j.c. ,wiggins k.l. ,heckbert s.r. ,hammond c.j. ,andrew t. ,fahy s. ,attia j. ,holliday e.g. ,scott r.j. ,islam f.m.a. ,rotter j.i. ,mcauley a.k. ,boerwinkle e. ,tai e.s. ,gudnason v. ,siscovick d.s. ,vingerling j.r. ,wong t.y.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 10 - صفحه:1 -12
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چکیده
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There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. we performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. we analyzed data from four population-based discovery cohorts with 15,358 unrelated caucasian individuals,who are members of the cohort for heart and aging research in genomic epidemiology (charge) consortium,and replicated findings in four independent caucasian cohorts (n = 6,652). all participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. in the discovery cohorts,179 single nucleotide polymorphisms (snp) spread across five loci were significantly associated (p<5.0×10-8) with retinal venular caliber,but none showed association with arteriolar caliber. collectively,these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. four out of these five loci were confirmed in independent replication samples. in the combined analyses,the top snps at each locus were: rs2287921 (19q13; p = 1.61×10-25,within the rasip1 locus),rs225717 (6q24; p = 1.25×10-16,adjacent to the vta1 and nmbr loci),rs10774625 (12q24; p = 2.15×10-13,in the region of atxn2,sh2b3 and ptpn11 loci),and rs17421627 (5q14; p = 7.32×10-16,adjacent to the mef2c locus). in two independent samples,locus 12q24 was also associated with coronary heart disease and hypertension. our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber,an endophenotype of the microcirculation associated with clinical cardiovascular disease. these data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.
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آدرس
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department of epidemiology,erasmus medical center,rotterdam,netherlands,department of ophthalmology,erasmus medical center,rotterdam,netherlands,department of neurology,erasmus medical center,rotterdam, Netherlands, centre for molecular epidemiology,yong loo lin school of medicine,national university of singapore, Singapore, cardiovascular health research unit,university of washington,seattle,wa,united states,department of epidemiology,university of washington,seattle,wa, United States, division of epidemiology and clinical applications,national eye institute,national institutes of health,bethesda,md, United States, centre for eye research australia,university of melbourne,royal victorian eye and ear hospital,melbourne, Australia, department of epidemiology,erasmus medical center,rotterdam, Netherlands, centre for eye research australia,university of melbourne,royal victorian eye and ear hospital,melbourne,australia,centre for vision research,department of ophthalmology and the westmead millennium institute,university of sydney,sydney, Australia, department of ophthalmology and visual science,university of wisconsin,madison,wi, United States, department of ophthalmology and visual science,university of wisconsin,madison,wi, United States, department of epidemiology,erasmus medical center,rotterdam, Netherlands, centre for eye research australia,university of melbourne,royal victorian eye and ear hospital,melbourne, Australia, centre for vision research,department of ophthalmology and the westmead millennium institute,university of sydney,sydney, Australia, centre for vision research,department of ophthalmology and the westmead millennium institute,university of sydney,sydney, Australia, department of epidemiology,erasmus medical center,rotterdam,netherlands,department of internal medicine,erasmus medical center,rotterdam,netherlands,department of clinical chemistry,erasmus medical center,rotterdam, Netherlands, department of epidemiology,erasmus medical center,rotterdam,netherlands,department of internal medicine,erasmus medical center,rotterdam, Netherlands, department of epidemiology,erasmus medical center,rotterdam, Netherlands, netherlands institute of neuroscience,amsterdam,netherlands,department of ophthalmology,academic medical center,amsterdam, Netherlands, department of epidemiology,erasmus medical center,rotterdam, Netherlands, department of epidemiology,johns hopkins university bloomberg school of public health,baltimore,md, United States, department of ophthalmology,taipei veterans general hospital,taipei,taiwan,department of ophthalmology,national yang-ming university school of medicine,taipei, Taiwan, icelandic heart association,kopavogur,iceland,faculty of medicine,university of iceland,reykjavik, Iceland, cardiovascular health research unit,university of washington,seattle,wa,united states,department of medicine,university of washington,seattle,wa, United States, cardiovascular health research unit,university of washington,seattle,wa,united states,department of biostatistics,university of washington,seattle,wa, United States, cardiovascular health research unit,university of washington,seattle,wa,united states,department of biostatistics,university of washington,seattle,wa, United States, cardiovascular health research unit,university of washington,seattle,wa,united states,department of epidemiology,university of washington,seattle,wa,united states,department of medicine,university of washington,seattle,wa,united states,department of health services,university of washington,seattle,wa,united states,center for health studies,group health,seattle,wa, United States, department of ophthalmology,university of iceland,reykjavik,iceland,department of ophthalmology,landspitalinn university hospital,reykjavik, Iceland, icelandic heart association,kopavogur, Iceland, icelandic heart association,kopavogur,iceland,department of statistics,university of iceland,reykjavik, Iceland, laboratory of epidemiology,demography,and biometry,national institute on aging,national institutes of health,bethesda,md, United States, laboratory of epidemiology,demography,and biometry,national institute on aging,national institutes of health,bethesda,md, United States, medical genetics institute,cedars-sinai medical center,los angeles,ca, United States, medical genetics institute,cedars-sinai medical center,los angeles,ca, United States, department of epidemiology and biostatistics,case western reserve university,cleveland,oh, United States, department of epidemiology and biostatistics,case western reserve university,cleveland,oh, United States, department of epidemiology and biostatistics,case western reserve university,cleveland,oh, United States, centre for vision research,department of ophthalmology and the westmead millennium institute,university of sydney,sydney,australia,lions eye institute,university of western australia,centre for ophthalmology and visual science,perth, Australia, genetics and population health,queensland institute of medical research,brisbane, Australia, genetics and population health,queensland institute of medical research,brisbane, Australia, center for human genetics,duke university medical center,durham,nc, United States, cardiovascular health research unit,department of medicine,university of washington,seattle,wa, United States, cardiovascular health research unit,department of medicine,university of washington,seattle,wa, United States, center for health studies,group health,seattle,wa,united states,cardiovascular health research unit,department of epidemiology,university of washington,seattle,wa, United States, department of twin research and genetic epidemiology,king's college london school of medicine,st thomas' hospital,london, United Kingdom, department of twin research and genetic epidemiology,king's college london school of medicine,st thomas' hospital,london, United Kingdom, department of twin research and genetic epidemiology,king's college london school of medicine,st thomas' hospital,london, United Kingdom, school of biomedical sciences,university of newcastle,callaghan,australia,hunter medical research institute,newcastle, Australia, school of biomedical sciences,university of newcastle,callaghan,australia,hunter medical research institute,newcastle, Australia, school of biomedical sciences,university of newcastle,callaghan,australia,hunter medical research institute,newcastle, Australia, centre for eye research australia,university of melbourne,royal victorian eye and ear hospital,melbourne, Australia, medical genetics institute,cedars-sinai medical center,los angeles,ca, United States, centre for eye research australia,university of melbourne,royal victorian eye and ear hospital,melbourne, Australia, human genetics center and institute of molecular medicine,university of texas health science center at houston,houston,tx, United States, department of epidemiology and public health,yong loo lin school of medicine,national university of singapore,singapore,department of medicine,yong loo lin school of medicine,national university of singapore, Singapore, icelandic heart association,kopavogur,iceland,faculty of medicine,university of iceland,reykjavik, Iceland, cardiovascular health research unit,university of washington,seattle,wa,united states,department of epidemiology,university of washington,seattle,wa,united states,department of medicine,university of washington,seattle,wa, United States, department of epidemiology,erasmus medical center,rotterdam,netherlands,department of ophthalmology,erasmus medical center,rotterdam, Netherlands, centre for eye research australia,university of melbourne,royal victorian eye and ear hospital,melbourne,australia,singapore national eye centre and singapore eye research institute,singapore,department of ophthalmology,yong loo lin school of medicine,national university of singapore, Singapore
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Authors
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