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Gene marker increases celiac risk in young children; environment can’t be ignored

By Maggie Hennessy , 08-Jul-2014

Gene marker increases celiac risk in young children; environment can’t be ignored

A study published in the New England Journal of Medicine found that 26% of children with two copies of a high-risk variant in a specific group of genes develop an early sign of celiac disease called celiac disease autoimmunity (CDA) by age five. 

The study, conducted by The Environmental Determinants of Diabetes in Youth consortium (TEDDY)—whose aim is to find the cause of type 1 diabetes, focused on children with a family history of autoimmune disease (as opposed to celiac specifically).

“The big news here is if you have two copies of the HLA gene group rather than one, your risk of developing celiac disease is much, much higher,” Alessio Fasano, MD, pediatric gastroenterologist and research scientist, told FoodNavigator-USA. “So you can tell who will be at a higher risk for celiac disease among kids with family history of autoimmune disorder.”

The celiac study followed 6,403 newborn children with either of two high-risk gene groups called HLA that are important for immune function—HLA-DR3-DQ2 or HLA-DR4-DQ8—to see who would develop celiac disease or CDA. These genes are involved in presenting gluten to immune cells; about 90% of celiac disease patients carry HLA-DR3-DQ2. Over five years, 291 of the participants developed celiac disease, while another 786 developed CDA.

The children with two copies of HLA-DR3-DQ2 had the highest likelihood of disease development by age 5. Of this group, 26% developed CDA by age 5 and 12% developed celiac disease. In those with one copy of HLA-DR3-DQ2, the risks of CDA and celiac disease by age 5 were 11%.

Like any autoimmune disease, celiac requires a predisposition—in this case HLA genes, said Dr. Fasano, who also founded the University of Maryland Center for Celiac Research in 1996. “Without those genes, you cannot develop celiac disease. They’re not sufficient though, because a third of the population have this gene and will never develop celiac disease.”  

Indeed, based on earlier research, the scientists expected to find lower rates of CDA and celiac disease in the US and Germany than in Sweden—finding that rates of CDA in Sweden were nearly double that of US rates. But they were surprised to learn that Sweden also had higher rates of CDA and celiac disease than Finland, which suggests that other factors besides genetic makeup can tilt the scale in favor of celiac disease.

“You need these genes, but there must be something in environment when you see a difference in these countries as the TEDDY researchers did,” Dr. Fasano said. “In my humble and biased opinion, there are many other cofounders—whether you were born vaginally or through caesarian section, whether you were breastfed, how often you took antibiotics as a child—all factors that on a specific genetic background can tilt you and increase your risk of developing celiac disease.”

Source: New England Journal of Medicine
DOI: 10.1056/NEJMoa1313977
“Risk of Pediatric Celiac Disease According to HLA Haplotype and Country
Authors: Edwin Liu, M.D., Hye-Seung Lee, Ph.D., Carin A. Aronsson, M.Sc., William A. Hagopian, M.D., Ph.D., Sibylle Koletzko, M.D., Ph.D., Marian J. Rewers, M.D., M.P.H., George S. Eisenbarth, M.D., Ph.D., Polly J. Bingley, M.D., Ezio Bonifacio, Ph.D., Ville Simell, M.Sc., and Daniel Agardh, M.D., Ph.D

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