Genetic Associations with “Blue Babies”

Image by Mariana Ruiz LadyofHats [Public domain], via Wikimedia Commons

By Bethann Hromatka, Ph.D.

New research suggests that a once-fatal congenital heart defect – sometimes called “blue baby syndrome” – is influenced by genetic factors that are broadly found in the general population.

Different heart malformations lead to poor oxygenation of the blood and a bluish discoloration of the skin, but the most common culprit (affecting three in 10,000 births) is a condition called tetralogy of Fallot (fah-LO), or TOF. Before the first heart surgery was pioneered for this condition in the mid 1940s, about 80 percent of affected children died before the age of ten.

Genetic Factors and non-genetic factors

Like most heart malformations that arise in the womb, it’s not possible to point to a single causative factor for TOF. A number of non-genetic factors increase risk – alcoholism and diabetes in the mother as well as poor nutrition and certain infections during pregnancy.

But there are also hints that TOF is more common in some families, raising the possibility that genetics also plays a role.

A new study on TOF

The new study led by Dr. Heather Cordell from the Institute of Genetic Medicine in Newcastle provides insight into the genetic underpinnings of TOF. Dr. Cordell and colleagues carried out the first genome-wide association study (GWAS) on this condition in around 1,600 people of European ancestry and found two genetic variants associated with TOF. Their findings were published in the journal Human Molecular Genetics.

The first variant is located in a region of chromosome 12 (12q24) that has previously been associated with numerous complex conditions including coronary artery disease and autoimmune disease. The second variant is located in a gene called GPC5 that encodes a protein called glypican 5.

Other previously identified variants

Previous studies have linked deletions near this gene with heart malformations including TOF.  A few other markers were also suggestively linked to TOF and it’s possible that future, larger studies might solidify their involvement.

This is the first study to suggest that common genetic factors in developing fetus play a role in TOF. Roughly 30 percent of people have at least one risky version of the SNPs discussed here, but each variant only increases risk slightly. Combine these genetic factors with environmental cues and the scale might tip towards TOF.

February is American Heart Month.