Association of lipin 1 gene polymorphisms with measures of energy and glucose metabolism
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Association of lipin 1 gene polymorphisms with measures of energy and glucose metabolism. / Loos, Ruth J F; Rankinen, Tuomo; Pérusse, Louis; Tremblay, Angelo; Després, Jean-Pierre; Bouchard, Claude.
In: Obesity, Vol. 15, No. 11, 11.2007, p. 2723-32.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Association of lipin 1 gene polymorphisms with measures of energy and glucose metabolism
AU - Loos, Ruth J F
AU - Rankinen, Tuomo
AU - Pérusse, Louis
AU - Tremblay, Angelo
AU - Després, Jean-Pierre
AU - Bouchard, Claude
PY - 2007/11
Y1 - 2007/11
N2 - OBJECTIVE: To examine the importance of lipin 1 (LPIN1) gene variation in energy and glucose metabolism. Transgenic animal models have shown that lipin, a protein encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue while decreasing energy expenditure and lipid oxidation in skeletal muscle. Lpin1 was identified as the mutated gene in the fatty liver dystrophy mouse, which exhibits lipin deficiency and features of human lipodystrophy.RESEARCH METHODS AND PROCEDURES: We genotyped five LPIN1 polymorphisms and tested for association with resting metabolic rate (RMR), fat oxidation, fasting plasma insulin and glucose concentration, and obesity-related phenotypes, including BMI, body fat percentage, sum of six skinfolds, and waist circumference in 712 subjects of the Quebec Family Study.RESULTS: The strongest results were generation-specific. In parents, RMR of the G/G IVS13 + 3333A>G homozygotes was 107 kcal/d higher than in A/A homozygotes and 39 kcal/d higher than in A/G heterozygotes (p = 0.0003). In offspring, carriers of the C allele of the IVS18 + 181C>T variant had significantly higher (p < 0.0003) insulin levels than T/T homozygotes. These associations remained significant after adjusting for multiple testing. Several other associations between body composition measures and the IVS18 + 181C>T variant were significant (p = 0.05 to 0.003), suggesting a strong pattern of relationships.DISCUSSION: These findings support the hypothesis that sequence variation in the LPIN1 gene contributes to variation in RMR and obesity-related phenotypes potentially in an age-dependent manner.
AB - OBJECTIVE: To examine the importance of lipin 1 (LPIN1) gene variation in energy and glucose metabolism. Transgenic animal models have shown that lipin, a protein encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue while decreasing energy expenditure and lipid oxidation in skeletal muscle. Lpin1 was identified as the mutated gene in the fatty liver dystrophy mouse, which exhibits lipin deficiency and features of human lipodystrophy.RESEARCH METHODS AND PROCEDURES: We genotyped five LPIN1 polymorphisms and tested for association with resting metabolic rate (RMR), fat oxidation, fasting plasma insulin and glucose concentration, and obesity-related phenotypes, including BMI, body fat percentage, sum of six skinfolds, and waist circumference in 712 subjects of the Quebec Family Study.RESULTS: The strongest results were generation-specific. In parents, RMR of the G/G IVS13 + 3333A>G homozygotes was 107 kcal/d higher than in A/A homozygotes and 39 kcal/d higher than in A/G heterozygotes (p = 0.0003). In offspring, carriers of the C allele of the IVS18 + 181C>T variant had significantly higher (p < 0.0003) insulin levels than T/T homozygotes. These associations remained significant after adjusting for multiple testing. Several other associations between body composition measures and the IVS18 + 181C>T variant were significant (p = 0.05 to 0.003), suggesting a strong pattern of relationships.DISCUSSION: These findings support the hypothesis that sequence variation in the LPIN1 gene contributes to variation in RMR and obesity-related phenotypes potentially in an age-dependent manner.
KW - Adiposity/genetics
KW - Adult
KW - Alleles
KW - Basal Metabolism/genetics
KW - Body Fat Distribution
KW - Energy Metabolism/genetics
KW - Fasting/metabolism
KW - Female
KW - Genotype
KW - Glucose/metabolism
KW - Humans
KW - Insulin/metabolism
KW - Male
KW - Middle Aged
KW - Nuclear Proteins/genetics
KW - Phenotype
KW - Phosphatidate Phosphatase
KW - Polymorphism, Single Nucleotide/genetics
U2 - 10.1038/oby.2007.324
DO - 10.1038/oby.2007.324
M3 - Journal article
C2 - 18070763
VL - 15
SP - 2723
EP - 2732
JO - Obesity
JF - Obesity
SN - 1930-7381
IS - 11
ER -
ID: 258453567