Heredity Plays Big Role In Heart Disease Risk Factors

“There aresome interesting ethnic differences in cardiovascular risk factors,including the fact that blacks tend to have higher HDL (high-densitylipoprotein) and lower triglycerides, which is an advantage, and wesuspect it is due to genetic influences,” says Dr. Catherine L. Davis,clinical health psychologist at the Medical College of Georgia.

Coronary artery disease rates in the United States are similar or lower in blacks yet blacks have higher mortality rates.

Dr.Davis and her colleagues at MCG’s Georgia Prevention Institute examinedheritability – the percentage of a variable attributable to genes – tobetter understand the influence of genetics and environment on hearthealth.

Heritability studies were enabled by data MCG iscollecting on 500 pairs of twins – blacks and whites, identical andfraternal – to determine whether environmental stress is a risk factorfor cardiovascular disease. Identical twins have identical genes andfraternal twins share about 50 percent of their genes, much like normalsiblings.

“Any differences between identical twins must be due tothe environment,” says Dr. Harold Snieder, genetic epidemiologist. “Soyou can quantify the part that is due to genetics,” he says, notingthat heritability provides an aggregate look at the effect of genes,many of which may still be unknown.

Across both races they foundthat lipid levels, which include so-called good cholesterol, HDL, andbad cholesterol, LDL, as well as triglycerides, are 60 percent to 80percent determined by genetics.

A separate study found heart ratevariability – the heart’s ability to respond to changing demands – washeritable and equally so, about 70 percent, among young blacks andwhites, Dr. Snieder says.

“We also were able to confirm thatblacks indeed showed a more favorable pattern of heart ratevariability,” he says. “If you have a lot of variability, it means yourheart is able to cope well with changing demands. The heart needs toadapt all the time in real life,” says Dr. Snieder.

“It’s a paradox,” Dr. Davis says. “It’s the opposite direction you would expect given the disparities in health outcomes.”

“We would have expected environmental influences to be more important in blacks,” adds Dr. Snieder. “We did not find that.”

Whatthey did find they hope will provide new insight and possibly new, moretargeted treatment strategies for a cross section of people with heartdisease.

“What we are very interested in is how these riskfactors for cardiovascular disease develop over time and to what extentthe development is influenced by genes and environment,” says Dr.Snieder, who plans on gathering longitudinal data on an even largerpercentage of the twins he’s following.

“Even having these genesdoesn’t make blacks into long-lived healthy people necessarily,” saysDr. Davis. “But maybe that link could help scientists develop medicinesthat target the protein that gene encodes, to help people who have hightriglycerides try to correct them or try to help them raise their HDL.”

Thelipid study, published in the October issue of Twin Research and HumanGenetics, included 106 black twins and 106 white twins. The heart ratevariability study, published in the October issue of the AmericanJournal of Cardiology, looked at 166 adolescents, 104 pairs of twinsand 11 individual twins.

A related candidate gene study,published in the October issue of Ethnicity and Disease, looked at ahandful of genes linked to obesity and implicated in lipid metabolismin mostly unrelated individuals: 413 health adolescents and youngadults who were 44 percent black and 53 percent male. Researcherswanted to explore the relationship between these genes and lipid levels– in general, lipid levels worsen when weight increases – as well asany racial differences, Dr. Davis says.

They found whites weremuch more likely to have a variation of the LDL receptor gene thatraises triglycerides. A mutation in a second candidate gene, ApoB,seemed to predict total cholesterol but the total varied with body massindex: heavier people were more affected by the gene. Those under age18 with the same ApoB variant had a higher total cholesterol. Theeffect of that variant wasn’t seen in adults, making researcherssuspect its activity might be tied to puberty. Also, a variant of TNFagene was linked to a lower HDL in men. “Women are known to have higherHDL levels than men,” Dr. Davis says. “This gene might be interactingwith sex hormones to influence men’s HDL levels and make them a bitlower.”

Co-authors on the studies include Dr. Xiaoling Wang, Dr.Snieder’s postdoctoral fellow; Dr. Frank A. Treiber, MCG vice presidentfor research and vice chair of basic research for the Department ofPediatrics; Dr. Julian F. Thayer, Emotions and QuantitativePsychophysiology Section, National Institute on Aging, GerontologyResearch Center, Baltimore; and Dr. Anastasia Illiadou, ClinicalEpidemiology Unit, Department of Medicine, Karolinska Institute,Karolinska University Hospital, Stockholm.