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Effects of Perilipin (PLIN) Gene Variation on Metabolic Syndrome Risk and Weight Loss in Obese Children and Adolescents

Abstract

Context: Genetic polymorphisms at the perilipin (PLIN) locus have been investigated for theirpotential utility as markers for obesity and metabolic syndrome (MS). We examined in obesechildren and adolescents (OCA) aged 7-14 yr the association of single-nucleotide polymorphisms(SNP) at the PLIN locus with anthropometric, metabolic traits, and weight loss after 20-wk multidisciplinarybehavioral and nutritional treatment without medication.Design: A total of 234 OCA body mass index (BMI 30.4 4.4 kg/m2; BMI Z-score 2.31 0.4)were evaluated at baseline and after intervention. We genotyped four SNPs (PLIN1 6209T3C,PLIN4 11482G3A, PLIN5 13041A3G, and PLIN6 14995A3T).Results: Allele frequencies were similar to other populations, PLIN1 and PLIN4 were in linkagedisequilibrium (D 0.999; P0.001). 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 high-density lipoprotein cholesterol (40 9 vs. 44 10 mg/dl; P 0.003) andhigher homeostasis model assessment for insulin resistance (4.02.3 vs. 3.52.1; P0.015). Minorallele A at PLIN4 was associated with MS risk (age and sex adjusted) hazard ratio 2.4 (95% confidenceinterval 1.1- 4.9) for genotype GA and 3.5 (95% confidence interval 1.2-9.9) for AA.After intervention, subjects carrying minor allele T at PLIN6 had increased weight loss (3.33.7 vs.1.93.4 kg; P0.002) and increased loss of the BMI Z-score (0.230.18 vs. 0.180.15; P0.003).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, whereasthe PLIN6 SNP was associated with better weight loss, suggesting that these polymorphisms maypredict outcome strategies based on multidisciplinary treatment for OCA. (J Clin Endocrinol Metab93: 4933-4940, 2008) (AU)

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