CHOP logoCongenital heart disease (CHD) an illness claiming at least one in 100 live births, ranges from tiny holes between heart chambers to life-threatening abnormal structures such as hypoplastic left-heart syndrome. The only means to treat this appears to be making the infant go through numerous complicated surgeries. The University of Michigan has apparently revealed a genetic variant on chromosome 5 that appears to strongly raise the risk of congenital heart disease.

The investigators gathered DNA samples from 300 children with CHD and 2,200 healthy children. A group of scientists then conducted the process of genotyping, wherein they were looking for gene variants also known as mutations in the DNA of genes in or near the ISL1 gene. They then compared the results and alleged that eight alternative spellings in DNA bases (single-nucleotide polymorphisms, or SNPs) raised the risk of CHD.

“This gene, ISL1, plays a key role in regulating early cardiac development, so there is a compelling biological reason for investigating it as a genetic risk factor for CHD,” explained Peter J. Gruber, MD, PhD, lead author, a pediatric cardiothoracic surgeon and developmental biologist at The Children’s Hospital of Philadelphia.

During the second stage of the study, specific DNA sequences were examined and the results were mapped out. They now aimed to determine the gene regions of interest in detail. The investigators further analyzed genes from a total of 1,344 children with CHD and 6,135 healthy controls. They then concluded that variants in the ISL1 gene had strong associations with CHD.

Stephen Gruber affirmed, “It was challenging to analyze how genetic variation contributes to complex congenital heart disease,” Stephen Gruber said. “We combined expertise in cardiology, epidemiology, genetics and developmental biology that led to an interesting discovery.”

It was discovered that within the gene, one SNP increased the risk for white children, but a different SNP elevated the risk for African-American children. The investigators enlightened that the gene findings do not directly affect treatment for children with CHD, but studying the molecular basis of heart disease seem to benefit the children. Claimed to be a novel discovery, the scientists’ further claim to aid children seeking treatment.

Studies may be conducted in the near future to ascertain the way a mutation causes a particular type of heart defect. It may further enable researchers to determine a gene variant affecting other organ systems. Investigators should also learn how a child will respond to surgery, and when or even perhaps how to best perform perioperative, intraoperative or postoperative care. Furthermore, understanding the molecular events in early development many aid in providing a more personalized medication.

The study is published online in the journal Public Library of Science One.