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Hope on the Horizon
PNAS Publication by CHORI Scientist Implicates Genes in Type 1 Diabetes

In a recent study published in Procedures of the National Academy of Sciences, CHORI scientist and Vice President of research Discovery Research for Roche Molecular Systems, Inc., Henry Erlich, PhD and his colleagues and collaborators at the Barbara Davis Diabetes Center provide compelling evidence for a set of genes that can predict extreme risk for type 1 diabetes (T1D).

Certain alleles at the HLA DR and DQ genes on chromosome six have long been identified as having the highest risk for T1D.

“This study proves that there are other genes in the HLA region in addition to the HLA-DR and DQ genes that contribute to genetic susceptibility,” says Dr. Erlich.

Dr. Erlich and his colleagues were able to identify those genes by combining standard analysis of HLA-DR/DQ alleles with analysis of what is referred to as HLA haplotype sharing among siblings.

“A haplotype is a segment of the chromosome that is made up of closely linked genetic variants,” explains Dr. Erlich. “Siblings can share either 0, 1, or 2 haplotypes.”

Utilizing data from the Diabetes Autoimmunity Study of the Young (DAISY), which began enrolling subjects in 1993, Dr. Erlich and his colleagues were able to analyze siblings of patients with diabetes for haplotype sharing and compare the analysis with the longitudinal information regarding progression to, or development of, T1D in the initially unaffected sibling.

The results of combining the analysis of haplotype sharing with standard HLA analysis for DR/DQ involvement were striking, with those children that had both the high risk DR-DQ alleles and that shared both HLA haplotypes with their diabetic sibling having a 55% risk of overt diabetes by the age of 12.

“The predictive value with haplotype sharing and HLA typing is remarkably high,” Dr. Erlich says. “It’s rare in a complex disease to have a genetic profile in which half of the people will get the disease.”

Nevertheless, that is the risk level associated with this particular gene constellation. While the predictive statistics are high, they also represent potentially good news. With the establishment of this technique of combined analyses, new avenues for preventative treatment are potentially opened.

As Dr. Erlich explains,“With haplotype sharing and HLA typing, you can end up with a very high predictive risk. This means that if the risk is sufficiently high, and if the treatment sufficiently benign, you can potentially identify a subpopulation that would be ideal for preventative clinical trials – before disease development.”

While such clinical trials may not be imminent, the new information provides hope for such possibilities, and researchers like Dr. Erlich continue to provide the clues that could lead to a cure.

PubMed Abstract

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Monday, May 16, 2011 11:33 PM

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