Chromosome 9p21 and poor glycemic control interact to determine disease odds, according to JAMA study.

Genetic variation on chromosome 9p21 has been associated with increased risk of coronary artery disease (CAD) in the general population. But those patients who additionally have type 2 diabetes are at an elevated risk.

Scientists at the Joslin Diabetes Center say there is a fourfold increase in the risk of this condition when patients with the described scenario also exhibit poor glycemic control.

The researchers conducted two studies, with one including 734 type 2 diabetes patients (322 with angiographically diagnosed CAD and 412 with no evidence of CAD) who were recruited between 2001 and 2006; the other study included 475 type 2 diabetes patients whose survival status was monitored from the time of 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 (rs2383206) and characterized for their long-term glycemic control by averaging measurements of hemoglobin A1c (HbA1c) 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 glycemic control, the odds for CAD among participants having two risk gene variants but not poor glycemic control was increased twofold, whereas the odds for CAD among study participants with the same genotype but poor glycemic control was increased fourfold.

The interaction was stronger when a measure of long-term glycemic control (seven-year average rather than most recent HbA1c) was used for participants having two risk gene variants and a history of poor glycemia and for participants with the same genotype but not long-term poor glycemia. A similar interaction between the 9p21 variant and poor glycemic control was observed with respect to the rate of death after 10 years.

The article appears in the November 26 issue of JAMA.

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