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Gene Type Associated with Higher Risk of Celiac Disease

By BiotechDaily International staff writers
Posted on 10 Jul 2014
Researcher have found that children born with 2 copies of a high-risk variant in a specific group of genes confers 26% chance of developing celiac disease autoimmunity (CDA), an early sign of celiac disease (CD), by age 5. They also found a higher celiac risk in Sweden than in the three other studied countries, even with the same genetic risk factors.

The Environmental Determinants of Diabetes in Youth consortium (TEDDY) is studying CD and type-1 diabetes because both are autoimmune diseases with some of the same genetic risk factors. CD (which stems from an immune reaction to gluten) occurs in just under 1% of the USA population, and is more common than type-1 diabetes. The celiac study followed 6,403 newborn children with either of two high-risk gene groups important for immune function—HLA-DR3-DQ2 or HLA-DR4-DQ8—to see who would develop CD or CDA. These genes are involved in presenting gluten to immune cells. Over five years, 291 developed CD, while another 786 developed CDA.

“By looking at the genes of the children who participated in TEDDY, we can now identify who among them is at highest risk for CD, and their parents and health care providers can monitor these children to detect the disease early,” said Beena Akolkar, PhD, project scientist for TEDDY at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; primary funder of TEDDY) of the US National Institutes of Health (NIH; Bethesda, MD, USA).

Researchers found that youth with 2 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 CD. In those with 1 copy of HLA-DR3-DQ2, the risks of CDA and CD by age 5 were 11% and 3%, respectively. About 90% of CD patients carry HLA-DR3-DQ2.

Based on earlier research, lower rates of CDA and CD were expected in the USA and Germany than in Sweden. Rates of CDA in Sweden were nearly double the USA rates. However, the researchers were surprised to discover that Sweden also had higher rates of CDA and CD than Finland. “We’ve long known that Sweden has a high incidence of CD, but we don’t yet know why. TEDDY’s unique structure of having the same protocol in several countries enables us to search for factors that trigger the disease,” said the paper’s senior author Daniel Agardh, MD, PhD, of Lund University in Sweden, “By studying similarities and differences between genes and environmental factors in these countries, we hope to pinpoint risk factors for the disease.” This study will include examining how diet affects bacteria in the gut and the immune system of children with differing genetic risks.

The primary goal of TEDDY is to find the causes of type-1 diabetes—why some children with high-risk genes for type-1 diabetes go on to develop the disease while others with the same genetic risk do not. “With research networks like TEDDY, NIH is actively seeking to understand how diseases like celiac and type-1 diabetes occur and, by using genetic screening and other tools, to develop a more personalized approach to disease prevention and treatment,” said NIDDK Director Griffin P. Rodgers, MD.

The study was reported by Liu E. et al. in the New England Journal of Medicine, July 3, 2014.

Related Links:

National Institutes of Health
The Environmental Determinants of Diabetes in Youth consortium (TEDDY)
Celiac disease 



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