Effects of perilipin (PLIN) gene variation on metabolic syndrome risk and weight loss in obese children and adolescents.
BACKGROUND
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 yr the association of single-nucleotide polymorphisms (SNP) at the PLIN locus with anthropometric, metabolic traits, and weight loss after 20-wk multidisciplinary behavioral and nutritional treatment without medication.


METHODS
A total of 234 OCA [body mass index (BMI = 30.4 +/- 4.4 kg/m(2); BMI Z-score = 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 high-density lipoprotein cholesterol (40 +/- 9 vs. 44 +/- 10 mg/dl; P = 0.003) and higher homeostasis model assessment for insulin resistance (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% confidence interval = 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 (3.3 +/- 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.


CONCLUSIONS
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 multidisciplinary treatment for OCA.
Deram
Sophie
S
Laboratory of Human Nutrition and Metabolic Disease-LIM-25 of HC-FMUSP, Avenida Doutor Arnaldo, 455, Room 4305, São Paulo-SP, Brazil, CEP 01246-903. sophiederam@usp.br
Nicolau
Christiane Y
CY
Perez-Martinez
Pablo
P
Guazzelli
Isabel
I
Halpern
Alfredo
A
Wajchenberg
Bernardo L
BL
Ordovas
Jose M
JM
Villares
Sandra M
SM
D000293:Adolescent; D000483:Alleles; D000886:Anthropometry; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D001938:Brazil / Q000453:epidemiology; D002352:Carrier Proteins; D002648:Child; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055105:Waist Circumference; D015431:Weight Loss / Q000235:genetics*
D002352:Carrier Proteins; D007328:Insulin; C000602978:PLIN1 protein, human; D000070778:Perilipin-1; D010750:Phosphoproteins