Common variations in perilipin gene, central obesity, and risk of type 2 diabetes in US women.
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 obesity status modified such associations.


METHODS
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 BMI 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 National Cholesterol Education Program Adult Treatment Panel III definition of waist circumference>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 nonobese (central) women, carriers of rs2289487, rs8179043, and rs894160 had significantly greater risk of type 2 diabetes, adjusting for diabetes risk factors (odds ratio (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% confidence interval (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.


CONCLUSIONS
Our data indicate that central obesity may modify the associations between PLIN variations and diabetes risk in women.
Qi
Lu
L
Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. nhlqi@channing.harvard.edu
Zhang
Cuilin
C
Greenberg
Andrew
A
Hu
Frank B
FB
D050153:Abdominal Fat; D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D002352:Carrier Proteins; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006306:Health Surveys; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics*; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D049629:Waist-Hip Ratio
D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins