How Can a Tasty Milkshake Increase the Risk of Heart Disease?

Drinking tasty milkshakes may be associated with increased risk of heart disease, found a genetic study. It was surprising that the Genetics of Lipid-lowering Drugs and Diet Network (GOLDN) included nearly 800 people in Minnesota and Utah, who consumed more than 1,500 milkshakes from 2002 to 2005 for a research study.

Among these self-sacrificing study subjects, few were under the microscope for about 25 years mainly to help the research team to assess the related cardiovascular risks.

The main objective of the study was to determine the role of genes that may

• influence the cholesterol levels after consuming high-fat meals
• affect the response to medication for lowering triglyceride and bad cholesterol

The study ultimately leads to a discovery of new uncommon gene variants which affect patient’s response to cholesterol drug, found the team of medical geneticists at the University of Texas Health Science Center at Houston, the University of Alabama at Birmingham, the University of Kentucky, and seven other institutions. The findings of the study were reported in the Journal of Lipid Research.

Atherosclerosis

High levels of cholesterol in the blood increase the accumulation of fat deposits to form a clog in the walls of the arteries, thereby increasing the risk of heart attacks and stroke. This process is known as atherosclerosis.

A high-fat diet and family history are common risk factors associated to increase the risk of developing heart disease.

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The level of triglycerides and cholesterol are related to the type of food consumed by an individual and whether they take cholesterol-lowering or lipid-lowering drugs. Every individual's cholesterol and triglyceride levels may not respond to the same diet and medications. Previous studies suggest that the differences in the drug and nutrition interactions may even be related to genetic factors inherited from parents, said the study's lead author, Xin Geng, a postdoctoral fellow at the University of Texas Health Science Center at Houston.

Several scientists have earlier identified the genetic variants that affect lipid responses. In the present study, the medical geneticists wanted to discover new uncommon gene variant.

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Details of the Study

The GOLDN participants were asked to come with an empty stomach. In the lab, they were provided with a milkshake which is made from a thick whipped cream, flavored with chocolate or strawberry syrup and crushed ice. Over four-fifths of the calories in the meal was from fat.

The blood test to measure high-density lipoprotein (good cholesterol), low-density lipoprotein (bad cholesterol) and triglycerides was done before and after the meal.

The participants were prescribed with fenofibrate, a medication that can reduce cholesterol and triglyceride levels, for three weeks. After three weeks, the participants were again provided with a milkshake, and blood test was assessed. The scientists also sequenced all of the genes in the participants' blood cells and examined the gene expression level.

Until now, it was believed that the common genetic variants mainly cause the variability in people's triglyceride and cholesterol levels, said Degui Zhi, senior author from UTHSC at Houston. But, it was found that common genetic variants revealed less than a quarter of inherited variability in triglyceride levels. The study hypothesis is that at least some of the 48 percent of unexplained variability could be driven by rare genetic variants that occur in below 5 percent of the population.

Findings of the Study

The research team found variants of at least three genes that were not very common in the study population but did relate to lipid changes in the people who had them.

"We found that variants in one gene, called SIPA1L2, predicted triglyceride level changes after consuming the milkshake. Variants in another gene, ITGA7, predicted LDL-cholesterol level ("bad" cholesterol) changes after taking the drug. And variants in a third gene, CEP72, predicted triglyceride response when comparing the pre-fenofibrate milkshake experiment to the post-fenofibrate milkshake experiment," said Ryan Irvin, another collaborator from UAB.

The team of researchers said that their findings should encourage other scientists to conduct further research studies to find additional rare gene variants, including non-protein-coding DNA that fell outside the scope of this study. They also insist that their study population was not vast, the GOLDN participants are mostly white. By studying for rare variants in different populations may also set up additional benefits in discovering new genes.

"Future studies can begin where we left off by trying to uncover exactly how the metabolic pathways and mechanisms these genes are part of interacting with dietary fat and fenofibrate to change triglyceride and cholesterol levels. Armed with this knowledge, we will be one step closer to finding new ways to prevent and treat unhealthy triglyceride and cholesterol levels," said Donna Arnett, dean of the UK College of Public Health and the GOLDN principal investigator.

Reference:

1. Xin Geng, Marguerite R. Irvin, Bertha Hidalgo, et al. An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort, Journal of Lipid Research (2018)DOI: 10.1194/jlr.P080333

Source-Medindia