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.
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.
Sparsø
Thomas
T
Steno Diabetes Center, 521, Niels Steensens Vej 2, 2820 Gentofte, Denmark. tspr@steno.dk
Hussain
Meena S
MS
Andersen
Gitte
G
Hainerova
Irena
I
Borch-Johnsen
Knut
K
Jørgensen
Torben
T
Hansen
Torben
T
Pedersen
Oluf
O
D000368:Aged; D016022:Case-Control Studies; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D050171:Dyslipidemias / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D047493:PPAR alpha / Q000235:genetics*; D011110:Polymorphism, Genetic; D019655:Quantitative Trait, Heritable; D044465:White People / Q000235:genetics
D047493:PPAR alpha