“Cholesterol in your blood is akin to smoking, and dietary choices can significantly increase the risk of cardiovascular disease,” said geneticist Helen Hobbs, who delivered a public lecture here on Friday.
Dr. Hobbs, who works at the University of Texas Southwestern Medical Centre, has been in India for most of this month and discussed her research on genetic mutations and their influence on heart disease as well as fatty liver disease. Her work has led to the development of a new class of drugs for the treatment of excessive cholesterol build-up and the prevention of coronary atherosclerosis (hardening and narrowing of arteries).
Dr. Hobbs, who won the 2016 Breakthrough Prize in Life Sciences, discovered a mutation in a gene called PCSK9, which particularly protects African-Americans against heart disease, and has this past month delivered public lectures explaining her work at Hyderabad and Bengaluru as part of the TNQ Distinguished Lectures in the Life Sciences.
The TNQ series has been bringing internationally renowned scientists face-to-face with the Indian scientific community since 2008.
The PCSK9 discoveries led to the development of PCSK9 inhibitors, said to be the most effective drugs to lower cholesterol — or low density lipoprotein (LDL) — since statins.
While most of her peers were focussed on genome-wide association studies, which involves finding variations in common genes, she opted to look for rare genes that dramatically influenced cholesterol levels.
Medical survey
She organised the Dallas Heart Study cohort that saw 6,000 residents of Dallas County, Texas, United States, aged 18 to 65 years, complete a detailed medical survey. A total of 3,500 participants over age 30 were invited to provide blood samples and to undergo comprehensive state-of-the-art imaging studies to assess plaque build-up in the blood vessels of the heart, the size and function of the heart, and the amount and distribution of body fat.
Following these patients for several years led to the discovery of rare mutations in the PCSK9 gene.
While the PCSK9 may be critical for a category of heart disease patients, Dr. Hobbs underlined that drugs were of limited utility if people had indulged in a lifetime of fatty food. “It is very important to start a healthy diet early,” she noted.
More recently, Dr. Hobbs’ team has identified genetic signatures that are associated with the full spectrum of alcoholic and non-alcoholic fatty liver disease, including steatosis, steatohepatitis, cirrhosis and hepatocellular carcinoma.
Dr. Hobbs and her team found that mutations in the protein PNPLA3 were strongly linked to this condition. Yet another screen showed that a mutation in TM6SF2 led to an increase in fat content. Dr. Hobbs’ team has shown that this protein helps the liver secrete fat into the blood in triglyceride-rich lipoproteins.
