Risky diet: Indians should keep away from fatty fast-food

For those who have ignored cholesterol and triglycerides and persisted with fat-loaded food, cigarette breaks, and exerciseless existence, a new blood test may yet spur a change in habits. Or so hopes Cyril Emmanuel, a cardiac geneticist in Chennai who?s trying to develop a genetic test to predict coronary artery disease among the young in India. The test is expected to look for mutations in specific genes believed to play a role in coronary artery disease. Emmanuel and his colleagues at the International Centre for Cardiothoracic and Vascular Diseases and the Postgraduate Institute of Basic Medical Sciences in Chennai have identified a mutation that may explain heart disease caused by blocked arteries among Indians below the age of 45.

Doctors have been concerned at the high incidence of coronary artery disease among young people in India. Studies here and in Western countries have shown that Indians tend to get coronary artery disease at lower ages than the Caucasians. While diet and lifestyle may be contributing to this cardiac epidemic, scientists have wondered whether genes are also to blame.

International studies have indeed hinted that dozens of genes might be involved in the development of coronary artery disease. Mutations in specific genes might raise or lower the risk of heart disease. Much of the research has focused on a group of genes that are involved in the removal of low-density lipoprotein (LDL) cholesterol, the so-called bad cholesterol, from the bloodstream. One gene implicated in coronary artery disease is the LDL receptor gene. The LDL receptor is a protein that helps remove LDL cholesterol from the blood. In the US, researchers Michael Brown and Joseph Goldstein decades ago showed that a mutation in the LDL receptor gene leads to hypercholesterolemia, a condition in which people have perpetually high levels of cholesterol, a discovery for which they shared the 1985 Nobel Prize. Mutations in a gene called Apolipoprotein B100 also make LDL stay in blood longer than usual. One version of the Apolipoprotein E gene makes people have higher than normal levels of cholesterol.

The Chennai team focused on a gene for an enzyme called angiotensin converting enzyme, or ACE. Over the past decade, a few foreign studies have suggested that a mutation in the ACE gene may be linked to coronary artery disease. ?However, the role of ACE gene has remained a controversy,? said Emmanuel. ?Its influence in coronary artery disease remains unresolved.?

But researchers know that ACE does play a key role in heart disease through its effect on the blood pressure. ACE generates a substance called angiotensin-II which causes blood vessels to narrow. ACE also inactivates another substance called bradykinin which dilates blood vessels. Through this ?double-effect,? ACE tends to raise the blood pressure.

Emmanuel took blood samples from 434 patients who were undergoing routine coronary angiography and 500 people with no history of heart disease, and analysed each of their ACE genes. The ACE gene is located on chromosome number 17. In some people, the gene carries a tiny segment of extra gene sequences called Alu. ?When Alu is present in the ACE gene, there is lower expression of ACE. The absence of Alu leads to higher expression of ACE. More ACE in the body means higher blood pressure which is detrimental from the point of view of coronary artery disease,? said Emmanuel.

The study showed that the absence of Alu was significantly associated with coronary artery disease, particularly a severe form called triple vessel disease in which the right coronary artery and two branches of the left coronary artery are blocked with fatty deposits. The increase in ACE levels in people with the Alu sequence absent may also lead to a decrease in insulin sensitivity which in turn can result in high blood glucose and diabetes. Reporting their findings in the journal Current Science, the Chennai scientists said this may explain why a significant number of the patients with triple-vessel disease had diabetes.

Analysing the ACE gene to determine whether Alu is present or not may thus become a predictive test for the risk of developing coronary artery disease, according to the Chennai researchers. The ACE gene is only the first among 40 genes that the researchers plan to study for associations with heart disease among Indians. ?The goal is to develop a diagnostic test based on many genes,? said Emmanuel. But top cardiologists caution that while genetic factors may indeed be at work in the genesis and progression of cardiovascular diseases, lifestyle-related factors remain significant as well as alterable. ?The dramatic decline in the incidence of coronary artery diseases in the West in recent years has been attributable to changes in lifestyle,? said Dr K. Srinath Reddy, head of cardiology, All India Institute of Medical Sciences, New Delhi.

Reddy said that though studies show that Indians are predisposed to low levels of good cholesterol, higher levels of the bad cholester-ol, particularly the fraction that causes a build-up of fatty deposits in the arteries, lead to abdominal obesity. But there are competing theories on why these features occur. While lack of activity can contribute to such features, some studies reveal a connection between inadequate exposure to nutrients during foetal life and heart disease in adulthood.