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The Identification of Genetic Hyperlipidemias Robert E.Ferrell , Ph.D

The Identification of Genetic Hyperlipidemias Robert E.Ferrell , Ph.D Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh. Click for larger picture. Table 114-9 Hyperlipidemic Disorders.

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The Identification of Genetic Hyperlipidemias Robert E.Ferrell , Ph.D

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  1. The Identification of Genetic Hyperlipidemias Robert E.Ferrell, Ph.D Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh

  2. Click for larger picture

  3. Table 114-9 Hyperlipidemic Disorders

  4. Table 114-9 Hyperlipidemic Disorders (Cont.)

  5. Table 114-9 Hyperlipidemic Disorders (Cont.)

  6. Click for larger picture

  7. Characteristics That May Identify An Individual with a Genetic Predisposition to Cardiovascular Disease Positive Family History Disease in a first-degree relative Parents, siblings Disease in female relatives Disease in the absence of other recognized risk factors Early age-at-onset Genetically determined risk often characterized by an earlier age-at onset Hyperlipidemia resistant to dietary intervention

  8. Table 120-4 Inbred populations with mutant LDL receptor alleles that account for >15% of the mutant alleles in that population Percent of FH Heterozygotes with mutation Inbred Population Mutation Christian Lebanon South African: Ashkenazi Jews Asian Indians Afrikaners FH Lebanese (C660X) FH Lithuania (G197del) FH Gujerat (P664L) FH Afrikaner-1 (D206E) FH Afrikaner-2 (V408M) 100 80 >15* 60-70 20-30

  9. Percent of FH Heterozygotes with mutation Inbred Population Mutation French Canada Iceland Finland Israel: Sephardic Jews Druze Ashkenazi Jews FH French Canadian-1 (del 5’ flanking region-intron 1) FH French Canadian-4 (W66G) FH Iceland (IVS4+2T>C) FH Helsinki (del exons 15-18) FH North Karelia (P288fs) FH Sephardic (D147H) FH Druze (Y167X) FH Lituania (G197del) 60 18 60 34 34 >15* >15* 35

  10. Percent of FH Heterozygotes with mutation Inbred Population Mutation FH Elverum (IVS3+1G>A) FH Genoa (D528G) FH Afrikaner-2 (V408M) E10X C122X FH French Canadian-4 (W66X) FH Cincinnati-5 (W23X)) 28 23 15 20 16 15 15 Norway Greece Spain Belgium (Sourthern) Denmark

  11. MAJORGENES POLYGENES Individual& Shared ENVIONMENT LDL-C [LDLR, APOB] FH FDB FCHL Dyslipidemia [LPL] Small Dense LDL Type III [APOE] HDL [APOAI] Apo A-1 [A-1 Milano] Lp(a) NIDDM IDDM H(e) [MTFHR, CS] Fibrinogen PAI-1 Platelet Glycoproteins Early HBP & CVA [GRA] [Liddle’s syndrome] [MEN-2] LDL-C [APOE]HDL-CBP [AGT]WeightOthers CigarettesOral Contraceptives Inactivity Stress Diet (Fat, calories, simple carbohydrates, Na, K, Cr, Mg, Ca, Folate, B6, B12, E, carotenoids, flavonoids, etc. ) Others Figure 24.1 Overlapping domains represent combined (additive or multiplicative) effects of monogenic, polygenic, and environmental factors promoting atherosclerosis.

  12. Figure 24.4 Coronary heart disease (CHD) incidence rates by family history and smoking status illustrate a multiplicative interaction, especially in the two younger age groups.

  13. Click for larger picture

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