ATHEROSCLEROSIS UPDATE 0
ATHEROSCLEROSE: LE POINT Canadian Atherosclerosis Society/Societe canadienne d'atherosclerose
Gene-environment interactions and atherosclerosis Robert A. Hegele, MD, FRCPC
cientific evidence supports the association be- associated risk factor was a high Lp(a) level. The tween serum lipid levels and atherosclerosis. Lp(a) level is not changed by diet or exercise, and The most solid evidence is found in patients only niacin and neomycin appear to lower it. The severity of the disease caused by some other with lipid phenotypes that have a proven biochemigenes appears to be modifiable by environmental cal and molecular basis.",2 Of course, some vegetariAn eight-generation Utah Mormon family factors.5'6 ans with "acceptable" cholesterol levels suffer myohas had many members with high LDL-C levels due cardial infarctions in their 30s, whereas other people, to a genetic LDL-receptor lesion.' The carriers of such as Sir Winston Churchill, seem to live forever despite personal stress, smoking, obesity and poor this genetic defect who lived in the 1800s survived 10 to 15 years longer than the carriers in this adherence to an approved diet. This can be explained by the difference in century. Serum levels of triglycerides, cholesterol, highthe Utah pioneers were physically active, lifestyle: density lipoprotein cholesterol (HDL-C) and lowand agrarian largely vegetarian. density lipoprotein cholesterol (LDL-C) neither exThe prevalence of extreme genetic resistance or clusively nor infallibly predict atherosclerosis. Other factors, including hypertension, carbohydrate intol- susceptibility to heart disease is around 5%. In the erance and increased thrombotic tendency, also play remaining 95% nature and nurture interact.1 There is a part. In addition, some environmental and genetic little doubt that a person's responses to environmenfactors appear to interact in complex ways to modu- tal factors can be determined by many genes. Once those genes and the nature of the genetic changes late cholesterol's effects. Some genes provide resistance to heart disease affecting these responses have been identified, there so strong that it may override environmental influ- may be a basis for early diagnosis of metabolic ences. For example, about 1 person in 200 with problems and individually tailored treatment. hypercholesterolemia has a genetically determined elevation of the HDL-C but not the LDL-C level.2 References This genetic condition clusters in families with histories of longevity, and diet seems to be irrelevant 1. Hegele RA, Breslow J: Apolipoprotein genetic variation in the assessment of atherosclerosis susceptibility. Genet Epidemiol to survival. Sir Winston may have been one of these 1987; 4:163-184 people. 2. Braslow JL: Genetic basis of lipoprotein disorders. J Clin Some genes confer exquisite sensitivity to heart Invest 1989; 84: 373-380 disease. This is true for some people with high levels 3. Breckenridge WC: Lipoprotein (a): Genetic marker for atherosclerosis? Can Med Assoc J 1990; 143: 115 of lipoprotein (a), or Lp(a). Lp(a) resembles LDL, Drayna DT, Hegele RA, Hass PE et al: Genetic linkage but it also has a linked plasminogen-like protein that 4. between lipoprotein (a) and DNA polymorphism at the plasappears to inhibit plasminogen activation at the site minogen gene. Genomics 1988; 3: 230-236 of a thrombus.3 The Lp(a) mass is genetically deter- 5. Hegele RA, Emi M, Wu LL et al: Clinical application of DNA markers in a Utah family with hypercholesterolemia. Am J mined, and plasma Lp(a) levels exceeding 0.52 Cardiol 1989; 63: 109-112 mmol/L (20 mg/dl) are associated with atherosclero- 6. Williams RR, Hunt SC, Wilson DE et al: Evidence that men sis. In one family half the men had myocardial with familial hypercholesterolemia can avoid early coronary infarctions in their early 40s;4 the only consistently death. JAMA 1986; 255: 219-224 Dr. Hegele is an assistant professor in the Department ofMedicine at the University of Toronto.
The opinions expressed in this article are those of the author and not necessarily those of the Canadian Atherosclerosis Society. Reprint requests to: Dr. Robert A. Hegele, St. Michael's Hospital, 30 Bond St., Toronto, Ont. M5B I W8 1332
CAN MED ASSOC J 1990; 143 (12)
ATHEROSCLEROSE: LE POINT Canadian Atherosclerosis Society/Societe canadienne d'atherosclerose
Gene-environment interactions and atherosclerosis Robert A. Hegele, MD, FRCPC
cientific evidence supports the association be- associated risk factor was a high Lp(a) level. The tween serum lipid levels and atherosclerosis. Lp(a) level is not changed by diet or exercise, and The most solid evidence is found in patients only niacin and neomycin appear to lower it. The severity of the disease caused by some other with lipid phenotypes that have a proven biochemigenes appears to be modifiable by environmental cal and molecular basis.",2 Of course, some vegetariAn eight-generation Utah Mormon family factors.5'6 ans with "acceptable" cholesterol levels suffer myohas had many members with high LDL-C levels due cardial infarctions in their 30s, whereas other people, to a genetic LDL-receptor lesion.' The carriers of such as Sir Winston Churchill, seem to live forever despite personal stress, smoking, obesity and poor this genetic defect who lived in the 1800s survived 10 to 15 years longer than the carriers in this adherence to an approved diet. This can be explained by the difference in century. Serum levels of triglycerides, cholesterol, highthe Utah pioneers were physically active, lifestyle: density lipoprotein cholesterol (HDL-C) and lowand agrarian largely vegetarian. density lipoprotein cholesterol (LDL-C) neither exThe prevalence of extreme genetic resistance or clusively nor infallibly predict atherosclerosis. Other factors, including hypertension, carbohydrate intol- susceptibility to heart disease is around 5%. In the erance and increased thrombotic tendency, also play remaining 95% nature and nurture interact.1 There is a part. In addition, some environmental and genetic little doubt that a person's responses to environmenfactors appear to interact in complex ways to modu- tal factors can be determined by many genes. Once those genes and the nature of the genetic changes late cholesterol's effects. Some genes provide resistance to heart disease affecting these responses have been identified, there so strong that it may override environmental influ- may be a basis for early diagnosis of metabolic ences. For example, about 1 person in 200 with problems and individually tailored treatment. hypercholesterolemia has a genetically determined elevation of the HDL-C but not the LDL-C level.2 References This genetic condition clusters in families with histories of longevity, and diet seems to be irrelevant 1. Hegele RA, Breslow J: Apolipoprotein genetic variation in the assessment of atherosclerosis susceptibility. Genet Epidemiol to survival. Sir Winston may have been one of these 1987; 4:163-184 people. 2. Braslow JL: Genetic basis of lipoprotein disorders. J Clin Some genes confer exquisite sensitivity to heart Invest 1989; 84: 373-380 disease. This is true for some people with high levels 3. Breckenridge WC: Lipoprotein (a): Genetic marker for atherosclerosis? Can Med Assoc J 1990; 143: 115 of lipoprotein (a), or Lp(a). Lp(a) resembles LDL, Drayna DT, Hegele RA, Hass PE et al: Genetic linkage but it also has a linked plasminogen-like protein that 4. between lipoprotein (a) and DNA polymorphism at the plasappears to inhibit plasminogen activation at the site minogen gene. Genomics 1988; 3: 230-236 of a thrombus.3 The Lp(a) mass is genetically deter- 5. Hegele RA, Emi M, Wu LL et al: Clinical application of DNA markers in a Utah family with hypercholesterolemia. Am J mined, and plasma Lp(a) levels exceeding 0.52 Cardiol 1989; 63: 109-112 mmol/L (20 mg/dl) are associated with atherosclero- 6. Williams RR, Hunt SC, Wilson DE et al: Evidence that men sis. In one family half the men had myocardial with familial hypercholesterolemia can avoid early coronary infarctions in their early 40s;4 the only consistently death. JAMA 1986; 255: 219-224 Dr. Hegele is an assistant professor in the Department ofMedicine at the University of Toronto.
The opinions expressed in this article are those of the author and not necessarily those of the Canadian Atherosclerosis Society. Reprint requests to: Dr. Robert A. Hegele, St. Michael's Hospital, 30 Bond St., Toronto, Ont. M5B I W8 1332
CAN MED ASSOC J 1990; 143 (12)
