Abnormal blood lipid levels play a significant role in the development of coronary artery disease (CAD).  The discovery of genomic variations that confer a protective effect against CAD has prompted investigations into the biological impact of these protective alleles.  Researchers have observed that specific single-base variations in the ANGPTL4 gene are common among patients with a low occurrence of CAD.  ANGPTL4 is located on chromosome 19 and codes for angiopoietin-like 4, a multifunctional glycosylated protein.One of the functions of angiopoietin-like 4 is the regulation of lipid metabolism.  Specifically, angiopoietin-like 4 inhibits the activity of the enzyme lipoprotein lipase (LPL).  Generally, active LPL is a homodimer consisting of two individual subunits that are each approximately 450 residues in length and weigh 50-kDa.  LPL functions on the surface of vascular endothelial cells to degrade the triglycerides of chylomicrons and very-low-density lipoproteins (VLDLs) in the blood.  Elevated triglyceride levels have been correlated with increased CAD risk.To identify common loss-of-function mutations in ANGPTL4, DNA samples from 43,000 individuals with CAD and 78,000 individuals without CAD were genotyped.  A detailed analysis of ANGPTL4 genomic variants was performed, and the results of individuals without CAD were mapped in Figure 1.  The lipid profiles of ANGPTL4 mutation noncarriers were also compared to those of mutation carriers (Figure 2).Figure 1  Loss-of-function mutations observed in the ANGPTL4 gene of participants without CAD (Note:  *  indicates mutation resulting in a truncated protein; † indicates substitution of a cytosine for its complementary base.)Figure 2  Mean plasma lipid levels for ANGPTL4 mutation carriers and noncarriers.  (Note:  LDL = low-density lipoprotein; HDL = high-density lipoprotein; error bars = standard deviation.)To further analyze the effect of ANGPTL4 on blood lipid levels, ANGPTL4 knockout mice and mice that constitutively express ANGPTL4 were created.  Researchers hypothesized that two of the four biological profiles shown in Table 1 would be observed in these mice.Table 1  Predicted Biological Profiles of ANGPTL4 Mouse Models Question 48A scientist studying the sequence of the LPL homodimer would most likely expect that:A.ribosomes must translate a total of 1,350 mRNA nucleotides into amino acids to form one 100-kDa LPL homodimer.B.ribosomes must translate a total of 2,700 mRNA nucleotides into amino acids to form one 100-kDa LPL homodimer.C.ribosomes must translate a total of 1,350 mRNA nucleotides into amino acids to form one 50-kDa LPL homodimer.D.ribosomes must translate a total of 2,700 mRNA nucleotides into amino acids to form one 50-kDa LPL homodimer.

Describe the role of the coronary arteries.

Other genetic polymorphismsThe between-genotype difference for the homozygotes (A/A vs. G/G) for the b2-adrenergic receptor Arg16Gly gene for the cardiovascular death endpoint reached significance (P=0.05) (Fig. 2). Selected other comparisons approached significance (aldosterone synthase promoter C-344T, C/Cvs. T/T, stroke, P=0.06; type 1 angiotensin receptor A11 66C, A/C vs. A/A, primary composite, P=0.07; bradykinin 2 receptor I/D, I/D vs. I/I, primary composite, P=0.07; and G protein b3-subunit C825T, C/T vs. C/C, MI, P=0.07). However, most of these did not seem biologically plausible because the effects were seen in heterozygotes only, and after adjusting for multiple testing of the many endpoints (comparison with Bonferroni-adjusted P value of 0.001), no between-genotype differences were significant, suggesting that these results are most likely chance findings.Genotype-by-treatment differences between losartan and atenolol for the cardiovascular endpoints were not significant (P values 0.06–0.98, Supplementary Table 4, Supplemental Digital Content 4, http://links.lww.com/FPC/A77), with the ex- ception of cardiovascular death for the b2-adrenergic receptor Gln27Glu genotype (P=0.02) (Supplemental Table 4d, Sup- plemental Digital Content 4, http://links.lww.com/FPC/A77). Again, this is likely a chance finding because the P values were not less than the Bonferroni-adjusted P value of 0.001.

Increased risk of heart disease is associated with elevated levels of which lipoprotein?

Which of the following is a risk factor for heart disease?Being overweightBeing underweightRegular exerciseLow cholesterol levels2In coronary heart disease:The heart beats too quicklyThe heart beats too slowlyThe heart valves do not work properlyThe arteries that supply blood to the heart muscle become narrow3Which of the following is a risk associated with fitting a stent?Blood lossRejectionThrombosis/blood clotRequires general anaesthetic 4Statins may be prescribed to anyone at risk of cardiovascular disease. They work by:Suppressing the immune systemReducing the production of cholesterol by the liverIncreasing the production of cholesterol by the liverBreaking down cholesterol5Doctors can operate and replace faulty heart valves. What is a disadvantage of using a mechanical rather than a biological valve? More likely to be rejected Requires anti-coagulation medicationDoes not last as longRequires a close tissue match6In heart transplant operations, what is an advantage of using a natural donor heart rather than an artificial heart?Less likely to be rejected Does not require life-long medicationLonger lastingGood availability

Which of the following controllable risk factors for coronary artery disease [CAD] appears most closely linked to the development of the disease? *1 pointA. AgeB. Medication usageC. High cholesterol levelsD. Gender