The complications of type 2 diabetes — damage to the kidneys, nerves, eyes, and cardiovascular system — result from chronically high blood sugar.
While routine blood tests can provide a snapshot of blood sugar levels at one point in time, a more complete picture of long-term blood sugar control is obtained by measuring the extent to which sugar molecules are attached to hemoglobin, the oxygen-carrying protein found in red blood cells.
Measurement of this “glycated hemoglobin” reflects the total amount of sugar blood cells have been exposed to over the preceding eight to 12 weeks.
Clinical trials have shown that elevated, yet sub-diabetic, glycated hemoglobin levels increase risk for type 2 diabetes and cardiovascular disease. But although many studies have looked for genetic variants associated with type 2 diabetes itself, much less work has been done to uncover the genetic determinants of glycated hemoglobin levels.
Guillaume ParÃ© and colleagues from Harvard Medical School and Amgen, Inc., scanned the genomes of more than 14,000 apparently healthy (i.e. non-diabetic women) to look for SNPs that correlate with glycated hemoglobin. Their results, published online today in PLoS Genetics, show that a variant in a gene never before linked to diabetes, HK1, is associated with glycated hemoglobin levels. Three other genes previously linked to diabetes and blood glucose concentration — GCK, SLC30A8 and G6PC2 — also harbored significantly associated variants.
According to the authors, the discovery of a link between the HK1 gene and glycated hemoglobin levels paves the way for further studies of the role of this gene in glucose metabolism and diabetes. The HK1 gene encodes the enzyme that carries out the first step of sugar breakdown in many cells throughout the body.
Together with the four variants, the researchers found to account for only a very small proportion of the total variance in glycated hemoglobin levels in the population — just 1.4%. Age, body mass index (BMI) and menopause status, on the other hand, explain about 9.5% of the variance.
Glycation of proteins in tissues other than red blood cells is thought to underlie the long-term complications of diabetes. The authors say it remains an open question whether the differences in glycated hemoglobin associated with the genetic variants identified in this study are paralleled in other parts of the body.
The SNPs associated with glycated hemoglobin levels are listed below by rsid#, gene, and the version associated with higher levels.