Scientists have found that genetic variation at the hexokinase-1 gene is linked to variation in the blood concentration of glycated hemoglobin, an index of long-term blood glucose concentration widely used in the follow-up of diabetes patients. The study, conducted by researchers from the Brigham and Women's Hospital in Boston, USA, is published December 19 in the open-access journal PLoS Genetics.
Diabetes is a leading cause of morbidity and mortality in both the developed and developing world. Because the main metabolic characteristic of diabetes is increased blood glucose concentration, the researchers sought to uncover the genetic determinants of glycated hemoglobin. Lead author Guillaume Paré and his team analyzed glycated hemoglobin concentration in a subset of 14,618 women from the Women's Genome Health Study, a large-scale study seeking to identify patterns of genetic variations that predict future disease states in otherwise healthy American women.
Using new technologies to study genetic variation on a whole genome basis, the group found that variations at the hexokinase-1 gene are an important determinant of glycated hemoglobin concentrations. Hexokinase-1 encodes the enzyme hexokinase, responsible for the first metabolic step in glucose utilization and a likely candidate for the control of glucose metabolism.
While further work will be needed to fully understand the metabolic role of these genetic variants, it is hoped that this discovery could lead to a better understanding of the mechanisms underlying diabetes and its complications.
This study was supported by the NIH as well as Amgen Inc.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.pgen.1000312 (link will go live on Friday, December 19)
CITATION: Pare´ G, Chasman DI, Parker AN, Nathan DM, Miletich JP, et al. (2008) Novel Association of HK1 with Glycated Hemoglobin in a Non-Diabetic Population: A Genome-Wide Evaluation of 14,618 Participants in the Women's Genome Health Study. PLoS Genet 4(12): e1000312. doi:10.1371/journal.pgen.1000312
Guillaume Pare, MD, M.Sc., FRCP(C)
Research Fellow, Harvard Medical School
Division of Preventive Medicine
Brigham and Women's Hospital
900 Commonwealth Avenue East,
3rd Floor Boston, MA 02215
TEL 617 525-6857
Cell 617 365-6310
FAX 617 734-1508
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