TY - JOUR

T1 - Relationships between the functional PPARalpha Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people

AU - Sparsø, Thomas

AU - Hussain, Meena S

AU - Andersen, Gitte

AU - Hainerova, Irena

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2007

Y1 - 2007

N2 - Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear receptor capable of regulating the expression of genes involved in peroxisomal and mitochondrial beta-oxidation pathways. The common Leu162Val polymorphism in the gene encoding PPARalpha has inconsistently shown association with quantitative traits related to obesity, type 2 diabetes, and dyslipidaemia. We genotyped the Leu162Val polymorphism in 1383 patients with type 2 diabetes and 4401 control subjects with normal glucose tolerance (NGT) without showing any association between diabetes and genotype. In addition, the Leu162Val polymorphism was not associated with WHO-defined obesity or dyslipidaemia in case-control settings involving 961 obese and 2563 lean subjects and 1399 dyslipidaemic and 4399 normolipidaemic subjects, respectively. Quantitative trait studies of metabolic variables were carried out in 5799 middle-aged, treatment-naïve subjects showing a difference in fasting serum triglyceride concentrations among homozygous Val-carriers (Leu/Leu+Leu/Val, n=5782, 1.33+/-1.35 mmol/l vs. Val/Val, n=17, 2.22+/-2.4 mmol/l, p=0.007). Similarly, Val/Val was associated with increased fasting serum total cholesterol concentrations (p=0.01). In conclusion, in a relative large-scale study of middle-aged whites we found no evidence of association between the PPARalpha Leu162Val polymorphism and obesity or type 2 diabetes. If replicated, the Val162Val variant may, however, confer an increase in fasting levels of serum lipids.

AB - Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear receptor capable of regulating the expression of genes involved in peroxisomal and mitochondrial beta-oxidation pathways. The common Leu162Val polymorphism in the gene encoding PPARalpha has inconsistently shown association with quantitative traits related to obesity, type 2 diabetes, and dyslipidaemia. We genotyped the Leu162Val polymorphism in 1383 patients with type 2 diabetes and 4401 control subjects with normal glucose tolerance (NGT) without showing any association between diabetes and genotype. In addition, the Leu162Val polymorphism was not associated with WHO-defined obesity or dyslipidaemia in case-control settings involving 961 obese and 2563 lean subjects and 1399 dyslipidaemic and 4399 normolipidaemic subjects, respectively. Quantitative trait studies of metabolic variables were carried out in 5799 middle-aged, treatment-naïve subjects showing a difference in fasting serum triglyceride concentrations among homozygous Val-carriers (Leu/Leu+Leu/Val, n=5782, 1.33+/-1.35 mmol/l vs. Val/Val, n=17, 2.22+/-2.4 mmol/l, p=0.007). Similarly, Val/Val was associated with increased fasting serum total cholesterol concentrations (p=0.01). In conclusion, in a relative large-scale study of middle-aged whites we found no evidence of association between the PPARalpha Leu162Val polymorphism and obesity or type 2 diabetes. If replicated, the Val162Val variant may, however, confer an increase in fasting levels of serum lipids.

KW - Aged

KW - Case-Control Studies

KW - Denmark

KW - Diabetes Mellitus, Type 2

KW - Dyslipidemias

KW - European Continental Ancestry Group

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Obesity

KW - PPAR alpha

KW - Polymorphism, Genetic

KW - Quantitative Trait, Heritable

U2 - 10.1016/j.ymgme.2006.10.007

DO - 10.1016/j.ymgme.2006.10.007

M3 - Journal article

C2 - 17129741

VL - 90

SP - 205

EP - 209

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 2

ER -