Researchers discover multiple genes associated with meconium ileus

Cystic fibrosis (CF) is a devastating disease caused by mutations in the CFTR gene. In Canada, one in every 3,600 children born has the disease.

Researchers have long been puzzled as to how individuals who carry the same CFTR mutations can experience such different courses of disease. Patients with CF are affected in multiple organs such as the lungs, pancreas and liver, to varying degrees.

An international team led by The Hospital for Sick Children (SickKids) and the University for Toronto (U of T) has found a potential answer to this puzzle. The team has discovered multiple genes associated with meconium ileus, a severe intestinal obstruction present at birth in 15 per cent of patients with CF. The study is published online in Nature Genetics.

"Because meconium ileus is inherited, present at birth, and subject to limited environmental influence, it provides an ideal focus for identifying other contributors beyond CFTR that could result in differences in CF disease," says the study's principal investigator Dr. Lisa Strug, a Scientist in Child Health Evaluative Sciences at the SickKids Research Institute and an Assistant Professor at the Dalla Lana School of Public Health at the University of Toronto.

The team studied the genomes of almost 4,000 CF patients from the International Consortium in Gene Modifiers of CF. They developed and implemented a novel statistical technique that incorporated information about the causal CFTR gene to identify other CF-related genes. Multiple genes associated with developing meconium ileus were identified as a consequence, and some of these genes are anticipated to influence disease in other CF-affected organs.

"This work highlights the benefit of integrating statistical methodology with other disciplines in scientific studies," says Dr. Lei Sun, an Associate Professor at the Dalla Lana School of Public Health and the Department of Statistics at U of T. Sun shares first-authorship on the study with Dr. Johanna Rommens, a Scientist in Genetics & Genome Biology at SickKids Research Institute and a Professor of Molecular Genetics at U of T.

"In cystic fibrosis, CFTR does not function normally, which causes disease," says Strug. "Identifying other genes that influence the degree of organ-specific CF disease suggests the possibility of personalized approaches to treatment for individuals with CF, as well as novel therapeutic targets."

"We are proud to support Dr. Strug's important cystic fibrosis research, allowing us to advance treatment, and bring us closer to finding a cure," said Maureen Adamson, Chief Executive Officer at Cystic Fibrosis Canada. "Cystic Fibrosis Canada plays a leading role in the worldwide race for a cure. In 2012/13, we will invest more than $7.5 million in innovative research and clinical care for Canadians living with this devastating disease and will fund 51 research projects, six targeted programs and partnerships, and 47 fellows and students."