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Genotypic Risk for Celiac Disease Early in Life

Summary and Comment |
July 2, 2014

Genotypic Risk for Celiac Disease Early in Life

  1. F. Bruder Stapleton, MD

Children who were homozygous for HLA haplotype DR3-DQ2 were at 5.7 times greater risk for celiac autoimmunity compared with children who had low-risk genotypes.

  1. F. Bruder Stapleton, MD

Celiac disease is an autoimmune condition that is associated with the presence of specific HLA haplotypes (DR3-DQ2 and DR4-DQ8) on chromosome 6. To determine the relative risk for developing celiac autoimmunity and celiac disease in children born with these haplotypes, investigators analyzed prospective data on 6403 children enrolled in an international study (The Environmental Determinants of Diabetes in the Young) before age 4.5 months.

At a median follow-up of 60 months, 786 children (12%) had developed celiac disease autoimmunity, defined as persistent presence of tissue transglutaminase (tTG) antibodies in consecutive blood tests taken at least 3 months apart. Small-intestine biopsies confirmed celiac disease in 291 of 350 children. In all, 312 children fulfilled all study criteria for the diagnosis of celiac disease; one fourth developed celiac disease before age 3 years.

Persistently high tTG antibody levels were found in 26% of children homozygous for the DR3-DQ2 HLA haplotype, compared with 11% of those with the DR3-DQ2/DR4-DQ8 haplotype. Nongenetic risk factors for celiac disease included having a first-degree relative with celiac disease, female sex, and residence in Sweden.

Comment

These data suggest that identification of the early development of celiac disease is possible. If and when personalized medicine becomes standard, this will be useful clinical information. The study is also the first, in my experience, to find any reason not to live in Sweden.

  • Disclosures for F. Bruder Stapleton, MD at time of publication Grant / research support NIH-NCI Editorial boards UpToDate

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