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och metabola medicinen. Om hypotesen om antagonistisk pleiotropi visar sig hållbar så kan den leda till att testbara hypoteser kan uppställas, bl.a. avseende lipidomsättning och dess markörer (ApoE4) och FH som här skildrats. Återigen bekräftas värdet av att väga in hur faktorer tidigt i livet (präglade av genetik och evolutionär selektion) kan ha betydelse för hälsa och sjukdom senare i livet enligt DoHAD konceptet (Developmental origins of Adult Health and Disease).29 Samtidigt ges här en möjlighet att på vissa punkter kunna möta kritikerna av kolesterolhypotesen på ett positivt sätt och erkänna att ett fokus på vuxen ohälsa och patientmaterial gjort många av oss blinda för att samma mekanismer kan betyda något annat tidigt i livet. Här möts således evolutionsmedicin, populationsgenetik, DoHAD, mikrobiota/parasit hypoteser för att förklara lipidrubbning i genesen till kardiovaskulär sjukdom på ett fruktbart sätt. Vetenskapen behöver

av och till nya impulser för att ställa kända problem under ny belysning. Tes och antites leder till en ny syntes. Kan det vara så? Vidare forskning får söka bättre svar än de vi har idag. Observera att dessa resonemang inte förtar värdet av en reglering av LDL kolesterol för att minska kardiovaskulär sjuklighet i vuxenlivet, eller hos barn och ungdomar med homozygot FH.24 Vi måste bara kunna erkänna de kunskapsluckor som trots allt finns och som denna artikel velat skildra. PETER M NILSSON Professor/överläkare, Institutionen för kliniska vetenskaper, samt Verksamhetsområde Internmedicin, Skånes universitetssjukhus, Malmö

Referenser 1. F  erence BA, Yoo W, Alesh I, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60(25):2631-9. 2. Nicholls SJ, Puri R, Anderson T, et al. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016; 316(22):2373-2384. 3. S abatine MS, Giugliano RP, Keech AC, et al; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med 2017;376:1713-1722. 4. Steg PG, Schwartz GG, Szarek M, et al. On behalf of the ODYSSEY OUTCOMES Investigators and Committees. ODYSSEY Outcomes: Cardiovascular Outcomes with Alirocumab after Acute Coronary Syndrome: Results of the ODYSSEY Outcomes Trial. (Late-breaker, oral presentation). 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Coupling ecology and evolution: malaria and the S-gene across time scales. Math Biosci. 2004;189(1):1-19. 15. A  zevedo OG, Bolick DT, Roche JK, et al. Apolipoprotein E plays a key role against cryptosporidial infection in transgenic undernourished mice. PLoS One. 2014;9(2):e89562. 16. M  itter SS, Oriá RB, Kvalsund MP, et al. Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil. Clinics (Sao Paulo). 2012;67(1):11-8. 17. T  rumble BC, Stieglitz J, Blackwell AD, et al. Apolipoprotein E4 is associated with improved cognitive function in Amazonian foragerhorticulturalists with a high parasite burden. FASEB J. 2017; 31(4):1508-1515. 18. Panizzon MS, Hauger R, Xian H, et al. Interaction of APOE genotype and testosterone on episodic memory in middle-aged men. Neurobiol Aging. 2014;35(7):1778.e1-8. 19. J  asienska G, Ellison PT, Galbarczyk A, et al. 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#3 2018

Min Medicin 2018 #3  
Min Medicin 2018 #3  
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