Alessandro Doria, MD, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, and colleagues examined the association of this genetic variant with CAD in individuals with type 2 diabetes and whether the association is affected by poor glycaemic control.

The researchers conducted 2 studies. The first study included 734 patients with type 2 diabetes (322 with angiographically diagnosed CAD and 412 with no evidence of CAD) who were recruited between 2001 and 2006. The second study included 475 patients with type 2 diabetes whose survival status was monitored from their recruitment between 1993 and 1996 until December 31, 2004.

Participants for both studies were tested for a representative single-nucleotide polymorphism of chromosome 9p21 and characterised for their long-term glycaemic control by averaging measurements of haemoglobin A1C taken in the years before study entry.

The researchers found that relative to the CAD risk for patients with neither a 9p21 risk gene variant nor poor glycaemic control, the odds for CAD among participants having 2 risk-gene variants but not poor glycaemic control was increased 2-fold, whereas the odds for CAD among study participants with the same genotype but poor glycaemic control were increased 4-fold.

The interaction was stronger when a measure of long-term glycaemic control was used for participants having 2 risk-gene variants and a history of poor glycaemia, and for participants with the same genotype but not long-term poor glycaemia.

A similar interaction between the 9p21 variant and poor glycaemic control was observed with respect to the rate of death after 10 years.

"In conclusion, 9p21 [variant] and poor glycaemic control interact in determining the odds of CAD in type 2 diabetes. This finding may have implications for our understanding of atherogenesis in diabetes and for the design of more effective prevention strategies," the authors wrote.

"More broadly, it illustrates the complex etiology of multifactorial disorders and highlights the importance of accounting for gene-environment and gene-gene interactions in the quest for genetic factors contributing to these conditions."

SOURCE: Journal of the American Medical Association

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