Submitted to: Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2007
Publication Date: 5/1/2008
Citation: Qi, L., Zhang, C., Greenberg, A.S., Hu, F.B. 2008. Common Variations in Perilipin Gene, Central Obesity, and Risk of Type 2 diabetes in US Women. Obesity. 16(5):1061-1065. Interpretive Summary: In this manuscript we investigated whether lean and obese women with increased amounts of abdominal fat, who either had or did not have specific alterations in the gene for the protein, perilipin, differed in their risk for developing diabetes. We found that lean women who had specific alterations in the gene for the protein, perilipin, had significantly increased risk of developing diabetes. However, in women who were obese and had increased levels of central abdominal fat, these specific gene alterations did not result in any further increased risk for developing type 2 diabetes. These studies suggest that lean women with specific alterations in the perilipin are at increased risk for developing type 2 diabetes. These studies and related studies will help us to identify individuals who are at increased risk of developing type 2 diabetes and develop nutritional strategies to protect these individuals from becoming diabetic.
Technical Abstract: Objective: The variations in perilipin gene (PLIN) were previously associated with obesity and insulin sensitivity. We examined whether PLIN variability was associated with diabetes risk and whether obesity status modified such associations. Research Methods and Procedures: We conducted a nested case-control study of 431 incident cases of type 2 diabetes and 791 healthy control women from the Nurses' Health Study. Obesity was defined by body mass index or waist circumference (central obesity). Results: In the sample of all participants, PLIN variations were not significantly associated with the incidence of diabetes. The central obesity status (By NCEP ATP III definition of waist circumference greater than 35 inches) significantly interacted with PLIN polymorphisms in relation to diabetes risk (P for interaction=0.027, 0.009, and 0.02 for rs2289487, rs8179043, and rs894160 respectively). In non-obese (central) women, carriers of rs2289487, rs8179043 and rs894160 had significantly greater risk of type 2 diabetes, adjusting for diabetes risk factors (OR=1.52, 1.03-2.25; 1.54, 1.07-2.23, and 1.57, 1.09-2.27 respectively). Haplotypes possessing the three polymorphisms were also significantly associated with diabetes risk (global test, P=0.01). As compared with the most common haplotype 111, haplotype 222 and 211 (1 codes the common and 2 codes the minor alleles) were associated with 44% (OR=1.44, 95% CI 1.09-1.91), P=0.01) and 70% (OR=1.70, 95% CI 1.04-2.77; P=0.03) greater risk respectively. The PLIN variations were not significantly associated with the disease risk among women with central obesity. Discussion: Our data indicate that central obesity may modify the associations between PLIN variations and diabetes risk in women.