Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/15/2008
Publication Date: 12/1/2008
Citation: Deram, S., Nicolau, C.Y., Perez-Martinez, P., Guazzelli, I., Halpern, A., Wajchenberg, B.L., Ordovas, J.M., Villares, S.M. 2008. Effects of Perilipin (PLIN) gene variation on metabolic syndrome risk and weight-loss in obese children and adolescents. Journal of Clinical Endocrinology and Metabolism. 93:4933-4940. Interpretive Summary: Obesity has been identified as "one of today’s most blatantly visible – yet most neglected – public health problems." This rising epidemic of overweight and obesity has been called by some as "globesity" to clearly reflect that is a global problem and that, unless action is taken, billions will suffer from debilitating conditions associated with this disorder. The prevalence of obesity is increasing especially among children and even more dramatic is the increase observed among minority populations. Changes in dietary and exercise patterns may be key factors for the development of obesity; however, genetic factors are also very important to predispose people to obesity as well as some of its consequences, such as diabetes. Moreover, genetic factors may also interact with certain type of diets in the development of obesity as well as in its successful prevention and therapy. We have examined the gene for perilipin (PLIN), a protein that coats intracellular lipid droplets and modulates fat cell lipolysis to investigate if different forms of the gene modulate the risk of diabetes and the response to a 20-week behavioral intervention in obese children in Brazil. We found that one form of the PLIN gene was associated with higher risk of diabetes in obese children, whereas another form of the gene was a predictor of more successful weight loss following a multi-disciplinary behavioral and nutritional treatment without medication. This research provides markers for early detection of obesity and diabetes and will be key for early prevention of these diseases before they become a major health burden later in life, compromising healthy aging.
Technical Abstract: Genetic polymorphisms at the Perilipin (PLIN) locus have been investigated for their potential utility as markers for obesity and Metabolic Syndrome (MS). We examined in obese children and adolescents (OCA) aged 7-14 years the association of single nucleotide polymorphisms (SNP) at the PLIN locus with anthropometric, metabolic traits, and weight-loss after 20-week multi-disciplinary behavioral and nutritional treatment without medication. Design: 234 OCA (BMI 30.4+/-4.4 kg/m2; BMI-Zscore 2.31+/-0.4) were evaluated at baseline and after intervention. We genotyped four SNPs (PLIN1 6209T>C, PLIN4 11482G>A, PLIN5 13041A>G, and PLIN6 14995A>T). Results: Allele frequencies were similar to other populations, PLIN1 and PLIN4 were in linkage disequilibrium (D’=0.999, p<0.001). At baseline, no anthropometric differences were observed, but minor allele A at PLIN4 was associated with higher triglycerides (111+/-49 vs. 94+/-42 mg/dL; P=0.003), lower HDL-C (40+/-9 vs. 44+/-10 mg/dL, P=0.003) and higher HOMA-IR (4.0+/-2.3 vs. 3.5+/-2.1 P=0.015). Minor allele A at PLIN4 was associated with MS risk (age and sex adjusted) hazard ratio 2.4 (95% CI 1.1-4.9) for genotype GA and 3.5 (95% CI 1.2-9.9) for AA. After intervention, subjects carrying minor allele T at PLIN6 had increased weight-loss (3.3+/-3.7 vs. 1.9+/-3.4 kg; P=0.002) and increased loss of the BMI-Z score (0.23+/-0.18 vs. 0.18+/-0.15; P=0.003). Due to group size, risk of by chance findings cannot be excluded. Conclusion: The minor A allele at PLIN4 was associated with higher risk of MS at baseline, whereas the PLIN6 SNP was associated with better weight-loss suggesting that these polymorphisms may predict outcome strategies based on multi-disciplinary treatment for OCA.