Association of the PRO12ALA polymorphism of the PPAR-gamma2 gene with oxidized low-density lipoprotein and cardiolipin autoantibodies in nondiabetic and type 2 diabetic subjects.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a key component in adipocyte differentiation and fat-specific gene expression and may modulate macrophage functions, like proinflammatory activities, and stimulate oxidized low-density lipoprotein (ox-LDL) uptake. We hypothesized that the Pro12Ala polymorphism of the PPAR-gamma2 gene may affect the immune response to ox-LDL. Therefore, we investigated the association of the Pro12Ala polymorphism of the PPAR-gamma2 gene with ox-LDL autoantibodies, as well anticardiolipin antibodies, in a 10-year prospective study. The Pro12Ala polymorphism was genotyped in 119 nondiabetic subjects (age, 45 to 64 years; body mass index [BMI], 19 to 46 kg/m(2)) and 70 type 2 diabetic patients (age, 45 to 65 years; BMI, 19 to 46 kg/m(2)) by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method. Ox-LDL autoantibodies and anticardiolipin antibodies were determined at baseline and after 10 years of follow-up. At baseline, the Pro12Ala polymorphism was not associated with ox-LDL autoantibodies in nondiabetic subjects, whereas type 2 diabetic patients having the Pro12Ala or the Ala12Ala genotypes tended to have higher levels of ox-LDL autoantibodies than did type 2 diabetic patients with the Pro12Pro genotype. At the 10-year follow-up, diabetic subjects having the Ala12 allele had higher ox-LDL autoantibody levels than did diabetic subjects with the Pro12Pro genotype (P =.043 after adjustment for age, gender, BMI, and hemoglobin A(1c) [HbA(1c)] at 5 years). In nondiabetic subjects and regarding anticardiolipin antibodies, no such relationship was observed. We conclude that the Pro12Ala polymorphism of the PPAR-gamma2 gene was associated with increased ox-LDL autoantibodies in type 2 diabetic subjects. Genotype may therefore modulate the oxidative modification of LDL in hyperglycemic milieu.
Niskanen
L
L
Department of Clinical Nutrition, and the A.I. Virtanen Institute of Molecular Sciences, University of Kuopio, Kuopio, Finland.
Lindi
V
V
Erkkilä
A
A
Sivenius
K
K
Luoma
J
J
Ylä-Herttuala
S
S
Laakso
M
M
Uusitupa
M I j
MI
D000409:Alanine; D017153:Antibodies, Anticardiolipin / Q000032:analysis*; D001323:Autoantibodies / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011392:Proline; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics*
D017153:Antibodies, Anticardiolipin; D001323:Autoantibodies; D008077:Lipoproteins, LDL; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C099252:oxidized low density lipoprotein; D011392:Proline; D000409:Alanine