Background: Currently, millions of individuals with high cholesterol take a similar type of drug, known as a statin. The drug, an inhibitor of HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase), the rate limiting enzyme in cholesterol biosynthesis, decreases blood levels of cholesterol by induce the expression of low density lipoprotein (LDL) receptors in the liver. The increased levels of the LDL-receptors stimulate the catabolism of plasma LDL, removing cholesterol from plasma, which is an important determinant of atherosclerosis. You may know of people who take a statin to help with their cholesterol levels. However, these drugs probably work slightly differently in many of those people. In some, it lowers their cholesterol significantly; in others it may lower it only moderately; and in some, it may have no significant effect at all. (Luckily for those individuals, there are multiple versions of the statins, so different drugs can be tested to find the proper combination for that individual.) Why the difference? Because of the genetic background of all people; the different single nucleotide polymorphisms that make us all different. Pharmacogenomics, a combination of pharmacology and genomics (the study of the genome) that refers to the study of the relationship between pharmaceuticals and genetics, may explain and simplify this problem.

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend takes more statins?
Answer: Brad

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend takes fewer statins?
Answer: Henry

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend takes an inhibitor of HMG-CoA reductase?
Answer: Brad

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend doesn't take an inhibitor of HMG-CoA reductase?
Answer: Henry

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend doesn't take a drug that decreases blood levels of cholesterol?
Answer: Henry

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend takes a drug that decreases blood levels of cholesterol?
Answer: Brad

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend takes a drug that induces the expression of low density lipoprotein (LDL) receptors in the liver?
Answer: Brad

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend does not take a drug that induces the expression of low density lipoprotein (LDL) receptors in the liver?
Answer: Henry

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend does not take a drug that removes cholesterol from plasma?
Answer: Henry

Situation: Brad and Henry were two old friends in their 70's. Brad had very high levels of cholesterol, while Henry was healthier and had normal levels of cholesterol.

Question: Which friend takes a drug that removes cholesterol from plasma?
Answer: Brad

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned more about an inhibitor of HMG-CoA reductase?
Answer: Kate

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned less about an inhibitor of HMG-CoA reductase?
Answer: Carol

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned less about rate limiting enzyme in cholesterol biosynthesis?
Answer: Carol

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned more about rate limiting enzyme in cholesterol biosynthesis?
Answer: Kate

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned less about inducing the expression of low density lipoprotein (LDL) receptors in the liver?
Answer: Carol

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned more about inducing the expression of low density lipoprotein (LDL) receptors in the liver?
Answer: Kate

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned more about stimulating the catabolism of plasma LDL?
Answer: Kate

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned less about stimulating the catabolism of plasma LDL?
Answer: Carol

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned less about removing cholesterol from plasma?
Answer: Carol

Situation: Two university students studied different types of drugs for their exams. Kate studied statins, while Carol studied anti-depressants.

Question: Which student learned more about removing cholesterol from plasma?
Answer: Kate

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle takes an inhibitor of HMG-CoA reductase?
Answer: Tom

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle doesn't take an inhibitor of HMG-CoA reductase?
Answer: Sam

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle doesn't take an inhibitor of the rate limiting enzyme in cholesterol biosynthesis?
Answer: Sam

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle takes an inhibitor of the rate limiting enzyme in cholesterol biosynthesis?
Answer: Tom

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle takes an inhibitor of the rate limiting enzyme that decreases blood levels of cholesterol?
Answer: Tom

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle doesn't take an inhibitor of the rate limiting enzyme that decreases blood levels of cholesterol?
Answer: Sam

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle doesn't take an inhibitor that induces the expression of low density lipoprotein (LDL) receptors in the liver?
Answer: Sam

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle takes an inhibitor that induces the expression of low density lipoprotein (LDL) receptors in the liver?
Answer: Tom

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle takes a drug that works slightly differently in many people?
Answer: Tom

Situation: Uncle Tom and uncle Sam both have high cholesterol. Uncle Tom is on statin drugs and uncle Sam is not.

Question: Which uncle doesn't take a drug that works slightly differently in many people?
Answer: Sam

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend started taking statins for his disease?
Answer: Ben

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend didn't start taking statins for his disease?
Answer: Andy

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend took a drug that changed the levels of HMG-CoA reductase?
Answer: Ben

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend didn't take a drug that changed the levels of HMG-CoA reductase?
Answer: Andy

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend didn't take a drug that changed the rate limiting enzyme in cholesterol biosynthesis?
Answer: Andy

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend took a drug that changed the rate limiting enzyme in cholesterol biosynthesis?
Answer: Ben

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend didn't take a drug that decreases blood levels of cholesterol?
Answer: Andy

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend took a drug that decreases blood levels of cholesterol?
Answer: Ben

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend took a drug that induces the expression of low density lipoprotein (LDL) receptors in the liver?
Answer: Ben

Situation: Ben and Andy were two old friends. They both have high levels of cholesterol. Ben was prescribed cholesterol medication, while Andy didn't go to the doctor because he was careless.

Question: Which friend didn't take a drug that induces the expression of low density lipoprotein (LDL) receptors in the liver?
Answer: Andy